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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 94 / 1))

Abstract

The N-nitroso compounds fall into the category of carcinogens discovered through proposed industrial use (Barnes 1974). In the early 1950s the then Director of the Medical Research Council’s Toxicology Research Unit, the late Dr. J.M.Barnes, was asked by Dr. H.Swaffield to investigate possible toxic hazards from the proposed use of a presumed relatively biologically inert, water- miscible, organic solvent, N-nitrosodimethylamine, (CH3)2N.NO (often referred to as dimethylnitrosamine; the systematic nomenclature is N-methyl-N-nitroso-methanamine). The stimulus was the finding by Dr. Swaffield that two men who had worked with this “new solvent” in a pilot plant had contracted cirrhosis of the liver.

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References

  1. Abbott PJ, Saffhill R (1979) DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O6 methylguanine. Biochim BiophysActa 562: 51–61.

    PubMed  CAS  Google Scholar 

  2. Albert RE, Burns FJ (1977) Carcinogenic atmospheric pollutants and nature of low level risks. In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of human cancer, book A. Cold Spring Harbor Laboratory, New York, pp 289–295.

    Google Scholar 

  3. Ames BN, Durston WE, Yamasaki E, Lee FD (1973) Carcinogens are mutagens: simple test system combining liver bacteria for detection. Proc Natl Acad Sci USA 70: 2281–2285.

    PubMed  CAS  Google Scholar 

  4. Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res 31: 347–364.

    PubMed  CAS  Google Scholar 

  5. Appel KE, Graf H (1982) Metabolic nitrite formation from jV-nitrosamines: evidence for acytochrome P-450 dependent reaction. Carcinogenesis 3: 293–296.

    PubMed  CAS  Google Scholar 

  6. Araki A, Muramatsu M, Matsushima T (1984) Comparison of mutagenicities of N-nitrosamines on Salmonella typhimurium TA100 and Escherichia coli WP2 UVRA/FKM 101 using rat and hamster liver S9. Gann 75: 8–16.

    PubMed  CAS  Google Scholar 

  7. Ashby J (1981) Triplet formed by three nitrosamines (NMorph, dPhNO and DNPT). In: De Serres FJ, Ashby J (eds) Evaluation of short-term tests for carcinogens. Elsevier/North-Holland, New York, pp 138–142.

    Google Scholar 

  8. Auerbach C, Robson JM (1946) Chemical production of mutations. Nature 157: 302.

    PubMed  CAS  Google Scholar 

  9. Bailey E, Connors TA, Farmer PB, Gorf SM, Rickard J (1981) Methylation of cysteine in hemoglobin following exposure to methylating agents. Cancer Res 41: 2514–2517.

    PubMed  CAS  Google Scholar 

  10. Barbacid M (1987) ras Genes. Ann Rev Biochem 56:779–827.

    Google Scholar 

  11. Barch DH, Fox CC (1987) Dietary zinc deficiency increases methylbenzylnitrosamine- induced formation of 06-methylguanine in oesophageal DNA of the rat. Carcinogenesis 8: 1461–1464.

    PubMed  CAS  Google Scholar 

  12. Bargmann CI, Hung M-C, Weinberg RA (1986) Multiple independent activation of neuoncogene by point mutation altering the transmembrane domain. Cell 45: 649–657.

    PubMed  CAS  Google Scholar 

  13. Barnes JM (1974) Nitrosamines. Essays in Toxicology 5: 1–15.

    CAS  Google Scholar 

  14. Barnes JM, Magee PN (1954) Some toxic properties of dimethylnitrosamine. Br J Ind Med 11: 167–174.

    PubMed  CAS  Google Scholar 

  15. Bartsch H, Malveille C, Camus AM, Martel-Planche G, Brun G, Hautefeuille A, Sabadie N, Barbin A, Kuroki T, Drevon C, Piccoli C, Montesano R (1980) Bacterial and mammalian mutagenicity tests: validation and comparative studies on 180 chemicals. In: Montesano R, Bartsch H, Tomatis L (eds) Molecular and cellular aspects of carcinogen screening tests. I ARC, Lyon, pp 179–241 (IARC scientific vol no 27 ).

    Google Scholar 

  16. Bartsch H, O’Neill IK, Schulte-Hermann R (1987) The relevance of N-nitroso compounds to human cancer: exposures and mechanisms. IARC, Lyon (IARC scientific publication no 84 ).

    Google Scholar 

  17. Belinsky SA, Walker VE, Maronpot RR, Swenberg J A, Anderson MW (1987) Molecular dosimetry of DNA adduct formation and cell toxicity in rat nasal mucosa following exposure to the tobacco-specific nitrosamine 4-(Ar-methyl-N-mtrosamine)-l-(3- pyridyl)-l-butanone and the relationship to induction of neoplasia. Cancer Res 47: 6058–6065.

    PubMed  CAS  Google Scholar 

  18. Beranek DT, Weiss CC, Swenson DH (1980) A comprehensive quantitative analysis of methylated and ethylated DNA using high pressure liquid chromatography. Carcinogenesis 1: 595–606.

    PubMed  CAS  Google Scholar 

  19. Berenblum I (1941) Co-carcinogenic action of croton resin. Cancer Res 1: 44–48.

    CAS  Google Scholar 

  20. Bohr VA, Okumoto DS, Hanawalt PC (1986) Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene. Proc Natl Acad Sci USA 83: 3830–3833.

    PubMed  CAS  Google Scholar 

  21. Boice JD Jr, Greene MH, Killen JY Jr, Ellenberg SS, Keehn RJ, McFadden E, Chen TT, Fraumeni JF Jr (1983) Leukaemia and pre-leukaemia after adjuvant therapy of gastro-intestinal cancer with semustine (methyl-CCNU). N Engl J Med 309: 1079–1084.

    PubMed  Google Scholar 

  22. Bos JL, Verlaande Vries M, Jansen AM, Veeneman GH, van Boom JH, van der Eb AJ (1984) Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization. Nucleic Acids Res 12: 9155–9163.

    PubMed  CAS  Google Scholar 

  23. Bos JL, Fearon ER, Hamilton SR, Verlaande Vries M, van Boom JH, van der Eb AJ, Vogelstein B (1987) Prevalence of ras gene mutations in human colorectal cancers. Nature 327: 293–297.

    PubMed  CAS  Google Scholar 

  24. Boyland E (1983) Surface active agents as tumour promoters. Environ Health Perspect 50: 347–350.

    PubMed  CAS  Google Scholar 

  25. Boyland E, Nice E, Williams K (1971) Catalysis of nitrosation by thiocyanate from saliva. Food Cosmetic Toxicol 9: 639–643.

    CAS  Google Scholar 

  26. Boyle JM, Margison GP, Saffhill R (1986) Evidence for excision repair of O6-n-butyldeoxyguanosine in human cells. Carcinogenesis 7: 1987–1990.

    PubMed  CAS  Google Scholar 

  27. Brambilla G, Cavanna M, Parodi S, Baldini L (1972) Induction of tumours in newborn and adult Swiss mice by N-diazoacetylglycine amide. Eur J Cancer 8: 127–129.

    PubMed  CAS  Google Scholar 

  28. Brennan RG, Pyzalska D, Blonski WJP, Hruska FE, Sundaralinjam M (1986) Crystal structure of the promutagen 04-methylthymidine: importance of the anti conformation of the 0(4) methoxy group and possible mispairing of 04-methylthymidine with guanine. Biochemistry 25: 1181–1185.

    PubMed  CAS  Google Scholar 

  29. Briscoe WH, Cotter L-E (1985) DNA sequence has an effect on extent and kinds of alkylation of DNA by a potent carcinogen. Chem Biol Interact 56: 321–331.

    PubMed  CAS  Google Scholar 

  30. Brookes P, Lawley PD (1960) Reaction of mustard gas with nucleic acids in vitro and in vivo. Biochem J 77: 478–484.

    PubMed  CAS  Google Scholar 

  31. Brookes P, Lawley PD (1964) Evidence for binding of polycyclic aromatic hydrocarbons to nucleic acids of mouse skin: relation between carcinogenic power of hydrocarbons and their binding to DNA. Nature 202: 781–784.

    PubMed  CAS  Google Scholar 

  32. Brooks JB, Cherry WB, Thacker L, Alley CC (1972) Analysis by gas chromatography of amines and nitrosamines produced in vivo and in vitro by Proteus mirabilis. J Infect Dis 126: 143–153.

    PubMed  CAS  Google Scholar 

  33. Bulbrook RD, Moore JW, Wang DY, Clark GMG (1984) Oestrogens and etiology and clinical course of breast cancer. In: Borzonyi M, Day NE, Lapis K, Yamasaki H (eds) Models, mechanisms and etiology of tumour promotion. IARC, Lyon, pp 385–395 (I ARC publication no 56 ).

    Google Scholar 

  34. Butterworth BE, Slaga TJ (eds) (1987) Nongenotoxic mechanisms in carcinogenesis. Cold Spring Harbor Laboratory, New York (Banbury Report no 25 ).

    Google Scholar 

  35. Casanova-Schmitz M, Starr TB, Heck H d’A (1984) Differentiation between metabolic in-corporation and covalent binding in labelling of macromolecules in rat nasal mucosa and bone marrow by inhaled [14C]- and [3H]formaldehyde. Toxicol Appl Pharmacol 76: 26–44.

    CAS  Google Scholar 

  36. Challis BC, Kyrtopoulos SA (1979) Nitrosation of amines by two-phase interaction of amines in solution with gaseous oxides of nitrogen. J Chem Soc Perkin Trans I, pp 299–304.

    Google Scholar 

  37. Challis BC, Fernandes MHR, Glover BR, Latif S (1987) Formation of diazopeptides by nitrogen oxides. In: Bartsch H, O’Neill IK, Schulte-Herman R (eds) The relevance of N-nitroso compounds to human cancer: exposures and mechanisms. I ARC scientific publication no 84. IARC, Lyon, pp 308–314.

    Google Scholar 

  38. Chan FPH, Ens B, Frei JV (1981) Cytogenesis of murine thymic lymphomas induced by N-methy 1-N-nitrisourea: difference in incidence of trisomy 15 in thymic lymphomas induced in neonatal and adult mice. Cancer Genet Cytogenet 4: 337–344.

    PubMed  CAS  Google Scholar 

  39. Chang MJW, Webb TE, Koestner A (1979) Distribution of O6-methylguanine in rat DNA following pretreatment in vivo with methylnitrosourea. Cancer Lett 6: 123–127.

    PubMed  CAS  Google Scholar 

  40. Chaw YFM, Crane LE, Lange P, Shapiro R (1980) Isolation and identification of crosslinks from formaldehyde-treated nucleic acids. Biochemistry 19: 5525–5531.

    PubMed  CAS  Google Scholar 

  41. Clanton DJ, Lu Y, Blair DG, Shih TY (1987) Structural significance of the GTP- binding domain of ras p21 studied by site-directed mutagenesis. Mol Cell Biol 7: 3092–3097.

    PubMed  CAS  Google Scholar 

  42. Cohen SM, Ellwein LB, Johansson SL (1987) Bladder tumour promotion. In: Butterworth BE, Slaga TJ (eds) Nongenotoxic mechanisms in carcinogenesis. Cold Spring Harbor Laboratory, New York, pp 55–68(Banbury Report no 25 ).

    Google Scholar 

  43. Connell JR, Medcalf ASC (1982) Induction of SCE and chromosomal aberrations with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-N- nitrosourea and dimethyl sulphate. Carcinogenesis 3: 385–390.

    PubMed  CAS  Google Scholar 

  44. Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M (1975) A model for gastric cancer epidemiology. Lancet 11: 58–60.

    Google Scholar 

  45. Coulondre C, Miller JH (1977) Genetic studies of the lac repressor. IV. Mutagenic specificity in the lac I gene of Escherichia coli. J Mol Biol 117: 577–606.

    Google Scholar 

  46. Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia colt Nature 274: 775–780.

    CAS  Google Scholar 

  47. Craddock VM (1971) Liver carcinomas in rats by single administration of dimethyl-nitrosamine after partial hepatectomy. JNCI 47: 899–905.

    Google Scholar 

  48. Craddock VM (1975) Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine, diethylnitrosamine and methyl methanesulphonate on liver regenerating after partial hepatectomy. I. Test for induction of liver carcinomas. Chem Biol Interact 10: 313–321.

    PubMed  CAS  Google Scholar 

  49. Craddock VM (1983) Nitrosamines and human cancer: proof of an association? Nature 306: 638

    PubMed  CAS  Google Scholar 

  50. Craddock VM (1987) Nutritional approach to oesophageal cancer in Scotland. Lancet 1: 217

    PubMed  CAS  Google Scholar 

  51. Craddock VM, Driver HE (1987) Sequential histological studies of rat oesophagus during rapid initiation of cancer by repeated injection of N-methyl-N-benzylnitrosamine. Carcinogenesis 8: 1129–1132.

    PubMed  CAS  Google Scholar 

  52. Craddock VM, Henderson AR (1984) Repair and replication of DNA in rat and mouse tissues in relation to cancer induction by N-nitroso-N-alkylureas. Chem Biol Interact 52: 223–231

    PubMed  CAS  Google Scholar 

  53. Craddock VM, Henderson AR (1986) Effect of N-nitrosamines carcinogenic for oesophagus on 06-alkylguanine-DNA-methyltransferase in rat oesophagus and liver. J Cancer Res Clin Oncol 111: 229–236

    PubMed  CAS  Google Scholar 

  54. Craddock VM, Henderson AR, Gash S (1982) Nature of constitutive and induced mammalian 06-methylguanine DNA repair system. Biochem Biophys Res Commun 107: 546–553.

    PubMed  CAS  Google Scholar 

  55. Craddock VM, Sparrow S, Henderson AR (1986) Effect of the trichothecene mycotoxin diaeetoxyscirpenol on nitrosamine-induced oesophageal cancer in the rat. Cancer Lett 31: 197–204.

    PubMed  CAS  Google Scholar 

  56. Crespi M, Ohshima H, Ramazzotti V, Munoz N, Grassi A, Casale V, Leclerc H, Calmels S, Cattoen C, Kaldor J, Bartsch H (1987) Intragastric nitrosation and precancerous lesions of the gastrointestinal tract: testing of an etiological hypothesis. In: Bartsch H, O’Neill IK, Schulte-Herman R (eds) The relevance of N-nitroso compounds to human cancer: exposures and mechanisms. IARC, Lyon, pp 511–517 (IARC scientific publication no 84 )

    Google Scholar 

  57. De Munter HK, Den Engelse L, Emmelot P (1979) Studies on lung tumours. N. Correlation between [3H]thymidine labelling of lung and liver cells and tumor formation in GRS/A and C3Hf/A male mice following administration of dimethyl- nitrosamine. Chem Biol Interact 24: 299–316.

    Google Scholar 

  58. Den Engelse L, Oomen LC, Van der Valk MA, Hart AA, Dux A, Emmelot P (1981) Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine-induced tumour formation in relation to H-2 haplotype. Int J Cancer 28: 199–208.

    CAS  Google Scholar 

  59. De Serres FJ, Ashby J (1981) Evaluation of short-term tests for carcinogens. Elsevier/North-Holland, New York, Chaps. 6, 11.

    Google Scholar 

  60. DeThe G, Ito Y (1978) Nasopharyngeal carcinoma: etiology and control. I ARC, Lyon (IARC scientific publication no 20 ).

    Google Scholar 

  61. Dipple A, Moschel RC, Bigger CAH (1984) Polynuclear aromatic hydrocarbons. In: Searle CE (ed) Chemical carcinogens, 2nd edn, part I. American Chemical Society, Washington DC, pp 41–163 (ACS Monograph no 182 ).

    Google Scholar 

  62. Dipple A, Michejda CJ, Weisburger EK (1987) Metabolism of chemical carcinogens. In: Grunberger D, Goff SP (eds) Mechanisms of cellular transformation by carcinogenic agents. Pergamon, Oxford, pp 1–32.

    Google Scholar 

  63. Doniger J, Notario V, DiPaolo JA (1987) Carcinogens with diverse mutagenic activities initiate neoplastic guinea pig cells that acquire the same N-ras point mutation. J Biol Chem 262: 3813–3819.

    PubMed  CAS  Google Scholar 

  64. Driver HE, White INH, Steren FS, Butler WH (1987) Possible mechanism for the dose- response relationship observed for renal mesenchymal tumours induced in the rat by a single dose of]V-nitrosodimethylamine. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) The relevance of N-nitroso compounds to human cancer: exposures and mechanisms. IARC, Lyon, pp 253–255.

    Google Scholar 

  65. Druckrey H (1975) Chemical carcinogenesis on N-nitroso derivatives. Gann Monographs Cancer Res 17: 107–132.

    CAS  Google Scholar 

  66. Druckrey H, Preussmann R (1962) Zur Entstehung carcinogener Nitrosamine am Beispiel des Tabakrauchs. Naturwiss 49: 498.

    CAS  Google Scholar 

  67. Druckrey H, Preussmann R, Ivankovic S, Schmidt CH, Mennel HD, Stahl KW (1964) Selective Erzeugung von Blasenkrebs an Ratten durch Dibutyl- und N-Butyl-N- butanol(4)-nitrosamin. Z Krebsforschung 66: 280–290.

    CAS  Google Scholar 

  68. Druckrey H, Ivankovic S, Preussmann R (1966) Teratogenic and carcinogenic effects in offspring after single injection of ethylnitrosourea to pregnant rats. Nature 210: 1378–1379.

    PubMed  CAS  Google Scholar 

  69. Druckrey H, Preussmann R, Ivankovic S, Schmähl D (1967) Organotrope carcinogene Wirkungen bei 65 verschiedenen N-nitroso-Verbindungen an BP-Ratten. Z Krebsforschung 69: 103–201.

    CAS  Google Scholar 

  70. Dunn BP, Stich HF (1986) 32P-Postlabelling analysis of aromatic DNA adducts in human oral mucosa. Carcinogenesis 7: 1115–1120.

    Google Scholar 

  71. Eisenstadt E, Warren AJ, Porter J, Atkins D, Miller JH (1982) Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[c,J]pyrene induce base substitutions. Proc Natl Acad Sei USA 79: 1945–1949.

    CAS  Google Scholar 

  72. Elder JB, Ganguli PC, Gillespie JE (1979) Cimetidine and gastric cancer. Lancet 1: 1005.

    PubMed  CAS  Google Scholar 

  73. Ender F, Havre G, Helgebostad A, Koppang M, Madsen R, Ceh L (1964) Isolation and identification of a hepatotoxic factor in herring meal produced from sodium nitrate- preserved herring. Naturwiss 51: 637–638.

    CAS  Google Scholar 

  74. Farber E (1984) Cellular biochemistry of the stepwise development of cancer with chemicals: GHA Clowes memorial lecture. Cancer Res 44: 5463–5474.

    PubMed  CAS  Google Scholar 

  75. Farmer PB, Shuker DEG, Bird I (1986) DNA and protein adducts as indicators of in vivo methylation of nitrosatable drugs. Carcinogenesis 7: 49–52.

    PubMed  CAS  Google Scholar 

  76. Feldman MY (1973) Reactions of nucleic acids and nucleoproteins with formaldehyde. Prog Nucl Acid Res Mol Biol 13: 1–47.

    CAS  Google Scholar 

  77. Fialkow PJ (1979) Clonal origin of human tumors. Ann Rev Med 30: 135–143.

    PubMed  CAS  Google Scholar 

  78. Fleig WE, Fussgaenger RD, Ditschuneit H (1982) Pathological changes in a human subject chronically exposed to dimethylnitrosamine. In: Magee PN (ed) Nitrosamines and cancer. Cold Spring Harbor Laboratory, New York, pp 37–68 (Banbury Report no 12 )

    Google Scholar 

  79. Fong LYY, Lin HJ, Lee CLH (1979) Methylation of DNA in target and non-target organs of the rat with methylbenzylnitrosamine and dimethylnitrosamine. Int J Cancer 23: 679–682.

    PubMed  CAS  Google Scholar 

  80. Foy H, Kondi A (1984) The vulnerable oesophagus: riboflavin deficiency and squamous cell dysplasia of the skin and oesophagus. JNCI 72: 941–948.

    Google Scholar 

  81. Frei JV (1980) Methylnitrosourea induction of thymomas in AKR mice requires one or two “hits” only. Carcinogenesis 1: 721–723.

    PubMed  CAS  Google Scholar 

  82. Frei JV, Lawley PD (1976) Tissue distribution and mode of DNA methylation in mice by methyl methanesulphonate and N-methyl-N-nitro-N-nitrosoguanidine: lack of thymic lymphoma induction and low extent of methylation of target tissue DNA at 0-6 of guanine. Chem Biol Interact 13: 215–222.

    PubMed  CAS  Google Scholar 

  83. Frei JV, Lawley PD (1980) Thymomas induced by simple alkylating agents in C57BL/Cbi mice: kinetics of the dose-response. JNCI 64: 845–856.

    Google Scholar 

  84. Frei JV, Venitt S (1975) Chromosome damage in bone marrow of mice treated with the methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea in presence or absence of caffeine and its relationship with thymoma induction. Mutat Res 29: 89–96.

    Google Scholar 

  85. Frei JV, Swenson DH, Warren W, Lawley PD (1978) Alkylation of DNA in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N- nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma: some applications of high-pressure liquid chromatography. Biochem J 174: 1031–1034

    PubMed  CAS  Google Scholar 

  86. Freund HA (1937) Clinical manifestations and studies in parenchymatous hepatitis. Ann Intern Med 10:144–155 Friedberg EC ( 1985 ) DNA repair. Freeman, New York

    Google Scholar 

  87. Funato T, Yokota J, Salamoto H, Kameya T, Fukushima S, Ito N, Terada M, Sugimura T (1987) Activation of N-ras gene in a rat hepatocellular carcinoma induced by dibutyl- nitrosamine and butylated hydroxy toluene. Gann 78: 689–694.

    PubMed  CAS  Google Scholar 

  88. Fussgaenger RD, Ditschuneit H (1980) Lethal exitus of patient with N- nitrosodimethylamine poisoning 2.5 years following first ingestion and signs of intoxication. Oncology 37: 273–277.

    PubMed  CAS  Google Scholar 

  89. Garcia H, Lijinsky W (1972) Tumorigenicity of five cyclic nitrosamines in MRC rats. Z Krebsforsch 77: 257–261.

    CAS  Google Scholar 

  90. Goth R, Rajewsky MF (1974 a) Molecular and cellular mechanism associated with pulse- carcinogenesis in the rat nervous system by ethylnitrosourea: ethylation of nucleic acids and elimination rates of ethylated bases from DNA of different tissues. Z Krebsforschung 82: 37–64.

    Google Scholar 

  91. Goth R, Rajewsky MF (1974b) Persistence of 06-ethylguanine in rat brain DNA; correlation with nervous system-specific carcinogenesis by ethylnitrosourea. Proc Natl Acad Sci USA 71: 639–643

    PubMed  CAS  Google Scholar 

  92. Guerrero I, Villasante A, Corces V, Pellicer A (1985) Loss of normal N-ras allele in mouse thymic lymphoma induced by a chemical carcinogen. Proc Natl Acad Sci USA 82: 7810–7814

    PubMed  CAS  Google Scholar 

  93. Guerrero I, Villasante A, Diamond L, Berman JW, Newcomb EW, Steinberg JJ, Lake R, Pellicer A (1986) Oncogen activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea. Leuk Res 10: 851–858.

    PubMed  CAS  Google Scholar 

  94. Gupta RC (1987) 32P-Postlabelling assay to measure carcinogen-DNA adducts. Prog Exp Tumor Res 32:21–32.

    Google Scholar 

  95. Habs M, Schmähl D, Wiessler M (1978) Carcinogenicity of acetoxymethylmethyl- nitrosamine after subcutaneous, intravenous and intrarectal application in rats. Z Krebsforsch 91: 217–221.

    CAS  Google Scholar 

  96. Haddow A (1938) Cellular inhibition and the origin of cancer. Acta Unio Int Contra Can- crum 3: 342–352.

    Google Scholar 

  97. Hall CN, Daikin D, Viney N, Cook A, Kirkham JS, Northfield TC (1987) Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in man. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific vol no 84. IARC, Lyon, pp 527–530.

    Google Scholar 

  98. Hamilton A, Hardy HL (1949) Industrial toxicology, 2nd edn. Hoerber, New York, p 311

    Google Scholar 

  99. Hanski C, Lawley PD (1985) Urinary excretion of 3-methyladenine and 1-meth-ylnicotinamide by rats following administration of [methyl-14C]methyl methanesul-phonate and comparison with administration of [14C] methionine or formate. Chem Biol Interact 55: 225–234.

    PubMed  CAS  Google Scholar 

  100. Harris G, Lawley PD, Asbery LJ, Chandler PM, Jones MG (1983) Autoimmune haemolytic disease in mice after exposure to a methylating carcinogen. Immunology 49: 439–449.

    PubMed  CAS  Google Scholar 

  101. Heath DF (1962) Decomposition and toxicity of dialkylnitrosamines in rats. Biochem J 85: 72–91

    PubMed  CAS  Google Scholar 

  102. Hecht SS, Chen CB, Dong M, Ornaf RM, Hoffmann D (1977) Chemical studies on tobacco smoke: studies on nonvolatile nitrosamines in tobacco. Beitr Tabakforschung 9: 1–6.

    CAS  Google Scholar 

  103. Hecht SS, Castonguay A, Chung F-L, Hoffmann D, Stoner GD (1982) Recent studies on metabolic activation of cyclic nitrosamines. In: Magee PN (ed) Nitrosamines and human cancer. Cold Spring Harbor Laboratory, New York, pp 103–120 (Banbury Report no 12 )

    Google Scholar 

  104. Hecht SS, Carmella SG, Trushin N, Foiles PG, Lin D, Rubin JM, Chung F-L (1987) Investigations on molecular disometry of tobacco-specific N-nitrosamines. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific publications no 84. IARC, Lyon, pp 423–429.

    Google Scholar 

  105. Hein GE (1963) Reaction of tertiary amines with nitrous acid. J Chem Educ 40: 181–184.

    CAS  Google Scholar 

  106. Heller EP, Goldthwait DA (1983) Release of 3-methyladenine from linker and core DNA of chromatin by a purified DNA glycolase. Cancer Res 43: 5747–5753.

    PubMed  CAS  Google Scholar 

  107. Hennings H, Shores R, Wenk ML, Spangler EF, Tarone R, Yuspa SH (1983) Malignant conversion of mouse skin tumours is increased by tumour initiators and unaffected by tumour promoters. Nature 304: 67–69.

    PubMed  CAS  Google Scholar 

  108. Herron DC, Shank RC (1980) Methylated purines in human liver DNA after probable dimethylnitrosamine poisoning. Cancer Res 40: 3115–3117.

    Google Scholar 

  109. Heston WE (1950) Carcinogenic action of the mustards. JNCI 11: 415–423.

    Google Scholar 

  110. Heyting C, Van der Laken CJ, Van Raamsdonk W, Pool CW (1983) Immunohistochemical detection of O6-ethyldeoxyguanosine in rat brain after in vivo applications of N- ethyl-N-nitrosourea. Cancer Res 43: 2935–2941.

    PubMed  CAS  Google Scholar 

  111. Hicks RM, Wakefield JSU, Chowaniec J (1975) Evaluation of a new model to detect bladder carcinogens or cocarcinogens: results obtained with saccharin, cyclamate and cyclophosphamide. Chem-Biol Interact 11: 225–233.

    PubMed  CAS  Google Scholar 

  112. Hicks RM, Walter CL, Elsebai I, El Aasser A-B, El Merzabani M, Gough TA (1977) Demonstrations of nitrosamines in human urine: preliminary observations on a possible aetiology for bladder cancer in association with chronic urinary tract infections. Proc R Soc Med 70: 413–416.

    PubMed  CAS  Google Scholar 

  113. Hill MJ (1986) Microbes and human carcinogenesis. Arnold, London Ho JHC (1972) Nasopharyngeal carcinoma. Adv Cancer Res 15: 57–92.

    Google Scholar 

  114. Howe GM (1986) Global geocancerology: a world geography of human cancers. Churchill Livingstone, Edinburgh IARC (1976) Dinitrosopentamethylenetetramine. IARC, Lyon, pp 241–245 (IARC Monographs on evaluation of carcinogenic risk of chemicals to humans, vol 11 ).

    Google Scholar 

  115. IARC (1980) Some non-nutritive sweetening agents. IARC, Lyon (IARC Monographs on evaluation of carcinogenic risk of chemicals to humans, vol 22 ).

    Google Scholar 

  116. IARC (1982 a) AT-Nitrosodiphenylamine. IARC, Lyon, pp 213–225 (IARC Monographs on evaluation of carcinogenic risk of chemicals to humans, vol 27).

    Google Scholar 

  117. IARC (1982 b) Formaldehyde. IARC, Lyon, pp 345-389 (IARC Monographs on evaluation of the carcinogenic risk of chemicals to humans, vol 29) Jensen DE, Stelman GJ, Spiegel A (1987) Species differences in blood-mediated nitrosocimetidine denitrosation. Cancer Res 47: 353–359.

    Google Scholar 

  118. Karran P, Lindahl T, Ofsteng I, Evensen GB, Seeberg E (1980) Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase. J Mol Biol 140: 101–127.

    PubMed  CAS  Google Scholar 

  119. Kazikoe T, Wang T-T, Eng VWS, Furrer R, Dion P, Bruce WR (1979) Volatile N-nitrosa-mines in urine of normal donors and of bladder cancer patients. Cancer Res 39: 829–832.

    Google Scholar 

  120. Keefer LF, Fodor CH (1970) Facile hydrogen isotope exchange as evidence for a-nitrosamine carbanion. J Am Chem Soc 92: 5747–5748.

    CAS  Google Scholar 

  121. Keefer L, Lijinsky W, Garcia H (1973) Deuterium isotope effect on the carcinogenicity of dimethylnitrosamine in rat liver. JNCI 51: 299–302.

    Google Scholar 

  122. Kelly MG, O’Hara RW, Adamson RH, Gadekar K, Botkin CC, Reese WH, Kerber HT (1966) Induction of hepatic cell carcinoma in monkeys with N-nitrosodiethylamme. JNCI 36: 323–351.

    Google Scholar 

  123. Kennaway EL, Hieger I (1930) Carcinogenic substances and their fluorescent spectra. Br Med J 1: 1044–1046

    PubMed  CAS  Google Scholar 

  124. Kim S, Lotlikar PD, Chin W, Magee PN (1977) Protein-bound carboxymethyl ester as a precursor of methanol formation during oxidation of dimethylnitrosamine in vitro. Cancer Lett 2: 279–284.

    PubMed  CAS  Google Scholar 

  125. Kimbrough RD (1982) Pathological changes in human beings acutely poisoned by dimethylnitrosamine. In: Magee PN (ed) Nitrosamine and human cancer. Cold Spring Harbor Laboratory, New York, pp 25–49 (Banbury Report no 12 ).

    Google Scholar 

  126. Kleihues P, Lantos PL, Magee PN (1976) Chemical carcinogenesis in the nervous system. Int Rev Exp Pathol 15: 154–232.

    Google Scholar 

  127. Knowles MA, Eydmann ME, Proctor A, Padua RA, Roberts J (1987) N-Methyl-N-nitrosourea-induced transformation of rat urothelial cells in vitro is not mediated by activation of ras oncogenes. Oncogene 1: 143–148.

    Google Scholar 

  128. Knudson AG Jr (1985) Hereditary cancer, oncogenes and antioncogenes. Cancer Res 45: 1437–1443.

    PubMed  CAS  Google Scholar 

  129. Koepke SR, Kroeger-Koepke MB, Michejda CJ (1987) N-Nitrosomethylaniline: possible mode of DNA modification. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific publication no 84. IARC, Lyon, pp 68–70.

    Google Scholar 

  130. Krüger FW (1971) Metabolism of nitrosamines in vivo. I. Evidence for oxidation of aliphatic di-zz-alkylnitrosamines: simultaneous formation of 7-methylguanine besides 7-propyl- and 7-butylguanine after application of di-n-propyl or di-/2-butylnitrosamine. Z Krebsforsch 76: 145–154.

    Google Scholar 

  131. Krüger FW (1972) New aspects in metabolism of carcinogenic nitrosamines. In: Nakahara W, Takayama S, Sugimura T, Odashima S (eds) Topics in chemical carcinogenesis. University of Tokyo Press, Tokyo, pp 213–235.

    Google Scholar 

  132. Ladd KF, Archer MC, Newmark HL (1984) Increased endogenous nitrosation in smokers. In: O’Neill IK, Von Borstel RC, Miller CT, Long J, Bartsch H (eds) N-nitroso compounds: occurrence, biological effects and relevance to human cancer. IARC scientific publication no 57. IARC, Lyon, pp 811–817.

    Google Scholar 

  133. Lantos PL (1986) Development of nitrosourea-induced brain tumours with a special note on changes occurring during latency. Food Chem Toxicol 24: 121–127.

    PubMed  CAS  Google Scholar 

  134. Lawley PD (1973) Reaction of N-methyl-yV-nitrosourea with 32P-labelled DNA: evidence for formation of phosphotriesters. Chem Biol Interact 7: 127–130.

    PubMed  CAS  Google Scholar 

  135. Lawley PD (1976) Methylation of DNA by carcinogens: some applications of chemical analytical methods. In: Montesano R, Bartsch H, Tomatis L (eds) Screening tests in chemical carcinogenesis. IARC, Lyon, pp 181–208 (IARC scientific publication no 12 ).

    Google Scholar 

  136. Lawley PD (1984) Carcinogenesis by alkylating agents. In: Searle CE (ed) Chemical carcinogens, 2nd edn, vol 1. American Chemical Society, Washington DC, Chap. 7 (ACS Monograph no 182 ).

    Google Scholar 

  137. Lawley PD (1989) Mutagens as carcinogens: development of current concepts. Mutat Res 213: 3–25.

    PubMed  CAS  Google Scholar 

  138. Lawley PD, Brookes P (1961) Acidic dissociation of 7:9-dialkylguanines and its possible relation to mutagenic properties of alkylating agents. Nature 192: 1081–1082.

    PubMed  CAS  Google Scholar 

  139. Lawley PD, Brookes P (1968) Cytotoxicity of alkylating agents towards sensitive and resistant strains of Escherichia coli in relation to extent and mode of alkylation of cellular macromolecules and repair of alkylation lesions in DNA. Biochem J 109: 433–447.

    PubMed  CAS  Google Scholar 

  140. Lawley PD, Orr DJ (1970) Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N-nitro-N-nitrosoguanidine. Chem Biol Interact 2: 154–157

    PubMed  CAS  Google Scholar 

  141. Lawley PD, Shah SA (1972) Reaction of alkylating mutagens and carcinogens with nucleic acids: detection and estimation of a small extent of methylation of 06 of guanine by methyl methanesulphonate in vitro. Chem Biol Interact 5: 286–288.

    PubMed  CAS  Google Scholar 

  142. Lawley PD, Shah SA (1973) Methylation of DNA 3H-14C-methyl-labelled N-methyl-N-nitrosourea: evidence for transfer of the intact methyl group. Chem Biol Interact 7: 115–120.

    PubMed  CAS  Google Scholar 

  143. Lawley PD, Thatcher CJ (1970) Methylation of DNA in cultured mammalian cells by N-methyl-N-nitro-N-nitrosoguanidine. Biochem J 116: 693–707.

    PubMed  CAS  Google Scholar 

  144. Lawley PD, Wallick CA (1957) Action of alkylating agents on DNA and guanylic acid. Chem Ind p 633

    Google Scholar 

  145. Lawley PD, Warren W (1976) Removal of minor methylation products 7-methyladenine and 3-methyladenine from DNA of Escherichia coli treated with dimethyl sulphate. Chem Biol Interact 12: 211–220.

    PubMed  CAS  Google Scholar 

  146. Lawley PD, Orr DJ, Shah SA, Farmer PB, Jarman M (1973) Reaction products from N- methyl-N-nitrosourea and DNA containing thymidine residues: synthesis and identification of a new methylation product O4-methylthymidine. Biochem J 135: 193–201

    PubMed  CAS  Google Scholar 

  147. Lawley PD, Harris G, Phillips E, Irving W, Colaco CB, Lydyard PM, Roitt IM (1986) Repair of chemical carcinogen-induced damage in DNA of human lymphocytes and lymphoid cell lines - studies of the kinetics of removal of 06-methylguanine and 3- methyladenine. Chem Biol Interact 57: 107–121.

    PubMed  CAS  Google Scholar 

  148. Leung K-H, Archer MC (1984) Studies on the metabolic activation of ß-ketonitrosamines: mechanisms of DNA methylation by N-(2-oxopropyl)-N-nitrosoureas and N- acetoxymethyl-JV-(2-oxopropyl)amine. Chem Biol Interact 48: 169–179.

    PubMed  CAS  Google Scholar 

  149. Leung K-H, Archer MC (1985) Mechanism of DNA methylation by 7V-nitroso(2-oxopropyl)-propylamine. Carcinogenesis 6: 189–191.

    PubMed  CAS  Google Scholar 

  150. Lewis SE, Johnson FM, Skow LC, Popp D, Barnett LB, Popp RA (1985) A mutation in the ß-globin gene detected in the progeny of a female mouse treated with ethyl- nitrosourea. Proc Natl Acad Sci USA 82: 5829–5831.

    PubMed  CAS  Google Scholar 

  151. Li BFL, Reese CB, Swann PF (1987) Synthesis and characterization of oligodeoxynucleo-tides containing 4-0-methylthymine. Bichemistry 26: 1086–1093.

    CAS  Google Scholar 

  152. Likhachev AJ, Ivanov MN, Bresil H, Planche-Martel G, Montesano R, Margison GP (1983) Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamster and persistence of alkylated purines in DNA of various tissues. Cancer Res 43: 829–833.

    PubMed  CAS  Google Scholar 

  153. Lijinsky W (1986) Deuterium isotope effects in carcinogenesis by N-nitroso compounds and related carcinogens. J Cancer Res Clin Oncol 112: 229–239.

    PubMed  CAS  Google Scholar 

  154. Lijinsky W (1987) Structure-activity relations in carcinogenesis by N-nitroso compounds. Cancer Metastasis Rev 6: 301–356.

    PubMed  CAS  Google Scholar 

  155. Lijinsky W (1988) Nucleic acid alkylation by jV-nitroso compounds related to organ-specific carcinogenesis. In: Politzer PA, Roberts L (eds) Chemical carcinogens: activation mechanisms, structural and electronic factors and reactivity. Elsevier, New York

    Google Scholar 

  156. Lijinsky W, Reuber MD (1984) Comparison of nitrosocimetidine with nitrosomethyl-nitroguanidine in chronic feeding tests in rats. Cancer Res 44: 447–449.

    PubMed  CAS  Google Scholar 

  157. Lijinsky W, Ross AE (1969) Alkylation of rat liver nucleic acids not related to carcinogenesis by N-nitrosamines. JNCI 42: 1095–1100.

    Google Scholar 

  158. Lijinsky W, Loo J, Ross A (1968) Mechanism of alkylation of nucleic acids by nitrosodimethylamine. Nature 218: 1174–1175.

    PubMed  CAS  Google Scholar 

  159. Lijinsky W, Saavedra JE, Reuber MD (1981) Induction of carcinogenesis in Fischer rats by methylalkylnitrosamines. Cancer Res 41: 1288–1292.

    PubMed  CAS  Google Scholar 

  160. Lijinsky W, Saavedra JE, Reuber MD, Singer SS (1982) Esophageal carcinogenesis in Fischer 344 rats by nitrosomethylethylamines substituted in the ethyl group. JNCI 68: 681–684.

    Google Scholar 

  161. Loeppky RN, Tomasik W, Ovtram JR, Kovacs DA, Byington KH (1984) Alternative bioactivation routes for ß-hydroxynitrosamines: biochemical and chemical model structures. IARC, Lyon, pp 429–136 (IARC scientific publication no 57 )

    Google Scholar 

  162. Mohr U, Green U, Althoff J, Schneider P (1978) Syncarcinogenic action of saccharin and sodium cyclamate in the induction of bladder tumours in N-methyl-N-nitrosourea- pretreated rats. In: Guggenheim B (ed) Health and sugar substitutes. Karger, Basel, pp 64–69.

    Google Scholar 

  163. Montesano R, Brésil H, Planche-Martel G, Margison GP, Pegg AE (1983) Stability and capacity of dimethylnitrosamine-induced O6-methylguanine repair system in rat liver. Cancer Res 43: 5808–5814.

    PubMed  CAS  Google Scholar 

  164. Moolgavkar SH, Knudson AG Jr (1981) Mutation and cancer: a model for human car¬cinogenesis. JNCI 66: 1037–1052.

    Google Scholar 

  165. Morimoto K, Tanaka A, Yamaha T (1983) Reaction of 1-propyl-1-nitrosourea with DNA in vitro. Carcinogenesis 4: 1455–1458.

    PubMed  CAS  Google Scholar 

  166. Morimoto K, Dolan ME, Scicchitano D, Pegg AE (1985) Repair of 06-propylguanine and 06-butylguanine in DNA by O6-alkylguanine-DNA alkyltransferase from rat liver and E. coli. Carcinogenesis 6: 1027–1031.

    CAS  Google Scholar 

  167. Moschel RC, Hudgins WR, Dipple A (1980) Aralkylation of guanosine by the carcinogen N-nitroso-N-benzylurea. Org Chem 45: 533–535.

    CAS  Google Scholar 

  168. Mottram JC (1945) Change from benign to malignant in chemically induced warts in mice. Br J Exp Pathol 26: 1–4.

    CAS  Google Scholar 

  169. Nicolson GL (1987) Tumor cell instability, diversification, and progression to the met-astatic phenotype: from oncogene to oncofetal expression. Cancer Res 47: 1473–1487.

    PubMed  CAS  Google Scholar 

  170. Nishimura S, Sekiya T (1987) Human cellular oncogenes. Biochem J 243: 313–327.

    PubMed  CAS  Google Scholar 

  171. Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46: 2203–2207.

    PubMed  CAS  Google Scholar 

  172. O’Connell JE, Klein-Szanto AJP, DiGiovanni DM, Fries JW, Slaga TJ (1986) Malignant progression of mouse skin papillomas treated with ethylnitrosourea, N-methyl-N- nitro-N-nitrosoguanidine, or 12-0-tetradecanoylphorbol-13-acetate. Cancer Lett 30: 269–274.

    PubMed  Google Scholar 

  173. O’Connor PJ, Capps MJ, Craig AW (1973) Comparative studies of the hepatocarcinogen N,N-dimethylnitrosamine in vivo: reaction sites in rat liver DNA and significance of their relative stabilities. Br J Cancer 27: 153–166.

    PubMed  Google Scholar 

  174. Ohshima H, Bartsch H (1981) Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in urine. Cancer Res 41: 3658–3662.

    PubMed  CAS  Google Scholar 

  175. Okada M, Suzuki E, Mochizuki M (1976) Possible important role of urinary N-methyl-N-(3-carboxypropyl)nitrosamine in induction of bladder tumors in rats by 7V-methyl-N-dodecylnitrosamine. Gann 67: 771–772.

    PubMed  CAS  Google Scholar 

  176. Olsson M, Lindahl T (1980) Repair of alkylated DNA in Escherichia coli: methyl group transfer from 06-methylguanine to a protein cysteine residue. J Biol Chem 255: 10569–10571.

    PubMed  CAS  Google Scholar 

  177. O’Neill IK, Von Borstel RC, Miller CT, Long J, Bartsch H (eds) (1984) N-Nitroso compounds: occurrence, biological effects and relevance to human cancer. IARC, Lyon (IARC scientific publication no 57 ).

    Google Scholar 

  178. Osborne MR (1984) DNA interactions of reactive intermediates derived from carcinogens. In: Searle CE (ed) Chemical carcinogens, 2nd edn. American Chemical Society, Washington DC, pp 503–507 (ACS Monograph no 182 ).

    Google Scholar 

  179. Osterman-Golkar S, Ehrenberg L, Segerback D, Hallstrom I (1976) Evaluation of genetic risks of alkylating agents. Hemoglobin as a dose monitor. Mutat Res 34: 1–10.

    Google Scholar 

  180. Oyasu R, Hirao Y, Izumi K (1981) Enhancement by urine of urinary bladder car-cinogenesis. Cancer Res 41: 478–481.

    PubMed  CAS  Google Scholar 

  181. Park KK, Archer MC, Wishnok JS (1980) Alkylation of nucleic acids by N-nitroso-di-propylguanine: evidence that carbonium ions are not significantly involved. Chem Biol Interact 29: 139–144.

    PubMed  CAS  Google Scholar 

  182. Park M, Dean M, Cooper CS, Schmidt M, O’Brien SJ, Blair DG, Vande Woude GF (1986) Mechanism of met oncogene activation. Cell 45: 895–904.

    PubMed  CAS  Google Scholar 

  183. Parsa I, Friedman S, Cleary CM (1987) Visualization of 06-methylguanine in target cell nuclei of dimethylnitrosamine-treated human pancreas by a murine monoclonal antibody. Carcinogenesis 8: 839–846.

    PubMed  CAS  Google Scholar 

  184. Pasternak L (1962) Mutagene Wirkung von Dimethylnitrosaminen bei Drosophila melanogaster. Naturwiss 49: 381.

    CAS  Google Scholar 

  185. Mohr U, Green U, Althoff J, Schneider P (1978) Syncarcinogenic action of saccharin and sodium cyclamate in the induction of bladder tumours in N-methyl-N-nitrosourea- pretreated rats. In: Guggenheim B (ed) Health and sugar substitutes. Karger, Basel, pp 64–69.

    Google Scholar 

  186. Montesano R, Brésil H, Planche-Martel G, Margison GP, Pegg AE (1983) Stability and capacity of dimethylnitrosamine-induced ö6-methylguanine repair system in rat liver. Cancer Res 43: 5808–5814.

    PubMed  CAS  Google Scholar 

  187. Moolgavkar SH, Knudson AG Jr (1981) Mutation and cancer: a model for human carcinogenesis. JNCI 66: 1037–1052.

    Google Scholar 

  188. Morimoto K, Tanaka A, Yamaha T (1983) Reaction of 1-«-propyl-1-nitrosourea with DNA in vitro. Carcinogenesis 4: 1455–1458.

    PubMed  CAS  Google Scholar 

  189. Morimoto K, Dolan ME, Scicchitano D, Pegg AE (1985) Repair of O6-propylguanine and 06-butylguanine in DNA by O6-alkylguanine-DNA alkyltransferase from rat liver and E. coli. Carcinogenesis 6: 1027–1031.

    PubMed  CAS  Google Scholar 

  190. Moschel RC, Hudgins WR, Dipple A (1980) Aralkylation of guanosine by the carcinogen N-nitroso-N-benzylurea. Org Chem 45: 533–535.

    CAS  Google Scholar 

  191. Mottram JC (1945) Change from benign to malignant in chemically induced warts in mice. Br J Exp Pathol 26: 1–4.

    CAS  Google Scholar 

  192. Nicolson GL (1987) Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res 47: 1473–1487.

    PubMed  CAS  Google Scholar 

  193. Nishimura S, Sekiya T (1987) Human cellular oncogenes. Biochem J 243: 313–327.

    PubMed  CAS  Google Scholar 

  194. Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46: 2203–2207.

    PubMed  CAS  Google Scholar 

  195. O’Connell JE, Klein-Szanto AJP, DiGiovanni DM, Fries JW, Slaga TJ (1986) Malignant progression of mouse skin papillomas treated with ethylnitrosourea, N-methyl-N- nitro-N-nitrosoguanidine, or 12-0-tetradecanoylphorbol-13-acetate. Cancer Lett 30: 269–274.

    PubMed  Google Scholar 

  196. O’Connor PJ, Capps MJ, Craig AW (1973) Comparative studies of the hepatocarcinogen N,N-dimethylnitrosamine in vivo: reaction sites in rat liver DNA and significance of their relative stabilities. Br J Cancer 27: 153–166.

    PubMed  Google Scholar 

  197. Ohshima H, Bartsch H (1981) Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in urine. Cancer Res 41: 3658–3662.

    PubMed  CAS  Google Scholar 

  198. Okada M, Suzuki E, Mochizuki M (1976) Possible important role of urinary N-methyl-N- (3-carboxypropyl)nitrosamine in induction of bladder tumors in rats by N-methyl-N-dodecylnitrosamine. Gann 67: 771–772.

    PubMed  CAS  Google Scholar 

  199. Olsson M, Lindahl T (1980) Repair of alkylated DNA in Escherichia coli: methyl group transfer from 06-methylguanine to a protein cysteine residue. J Biol Chem 255: 10569–10571

    PubMed  CAS  Google Scholar 

  200. O’Neill IK, Von Borstel RC, Miller CT, Long J, Bartsch H (eds) (1984) N-Nitroso compounds: occurrence, biological effects and relevance to human cancer. IARC, Lyon (IARC scientific publication no 57 ).

    Google Scholar 

  201. Osborne MR (1984) DNA interactions of reactive intermediates derived from carcinogens. In: Searle CE (ed) Chemical carcinogens, 2nd edn. American Chemical Society, Washington DC, pp 503–507 (ACS Monograph no 182 ).

    Google Scholar 

  202. Osterman-Golkar S, Ehrenberg L, Segerback D, Hallstrom I (1976) Evaluation of genetic risks of alkylating agents. Hemoglobin as a dose monitor. Mutat Res 34: 1–10.

    Google Scholar 

  203. Oyasu R, Hirao Y, Izumi K (1981) Enhancement by urine of urinary bladder carcinogenesis. Cancer Res 41: 478–481.

    PubMed  CAS  Google Scholar 

  204. Park KK, Archer MC, Wishnok JS (1980) Alkylation of nucleic acids by N-nitroso-di-propylguanine: evidence that carbonium ions are not significantly involved. Chem Biol Interact 29: 139–144.

    PubMed  CAS  Google Scholar 

  205. Park M, Dean M, Cooper CS, Schmidt M, O’Brien SJ, Blair DG, Vande Woude GF (1986) Mechanism of met oncogene activation. Cell 45: 895–904.

    PubMed  CAS  Google Scholar 

  206. Parsa I, Friedman S, Cleary CM (1987) Visualization of O6-methylguanine in target cell nuclei of dimethylnitrosamine-treated human pancreas by a murine monoclonal antibody. Carcinogenesis 8: 839–846.

    PubMed  CAS  Google Scholar 

  207. Pasternak L (1962) Mutagene Wirkung von Dimethylnitrosaminen bei Drosophila melanogaster. Naturwiss 49: 381

    CAS  Google Scholar 

  208. Pegg AE, Perry W (1981) Alkylation of nucleic acids and metabolism of small doses of dimethylnitrosamine in the rat. Cancer Res 41: 3128–3132.

    PubMed  CAS  Google Scholar 

  209. Penn I (1986) Malignancies induced by drug therapy: a review. In: Schmähl D, Daldo JM (eds) Carcinogenicity of alkylating drugs. IARC, Lyon, pp 13–27 (IARC scientific publication no 78 )

    Google Scholar 

  210. Perantoni AO, Rice JM, Reed CD, Watatani M, Wenk ML (1987) Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea. Proc Natl Acad Sci USA 84: 6317–6321.

    PubMed  CAS  Google Scholar 

  211. Peto R, Gray R, Brantom P, Grasso P (1984) Nitrosamine carcinogens in 5120 rodents. In: O’Neill IK, Von Borstel RC, Miller CT, Long J, Bartsch H (eds) IARC, Lyon, pp 627–665 (IARC scientific publication no 57 )

    Google Scholar 

  212. Pitot HC, Beer DG, Hendrich S (1987) Multistage carcinogenesis in the rat hepatocyte. In: Butterworth BE, Slaga TJ (eds) Nongenotoxic mechanisms in carcinogenesis. Cold Spring Harbor Laboratory, New York, pp 41–53 (Banbury Report no 25 ).

    Google Scholar 

  213. Poirier S, Hubert A, deThe G, Ohshima H, Bourgade M-C, Bartsch H (1987) Occurrence of volatile nitrosamines in food samples collected in three high-risk areas for nasopharyngeal carcinoma. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific vol no 84. IARC, Lyon, pp 415–419.

    Google Scholar 

  214. Popper H, Sternberg SS, Oser BC, Oser M (1960) Carcinogenic effect of aramite in rats. A study of hepatic nodules. Cancer 13: 1035–1045.

    Google Scholar 

  215. Pour P, Wallcave L, Gingell R, Nagel D, Lawson T, Salmasi S, Tines S (1979) Carcinogenic effect of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, a postulated proximate pancreatic carcinogen in Syrian hamsters. Cancer Res 39: 3828–3833.

    PubMed  CAS  Google Scholar 

  216. Preston-Martin S (1987) N-Nitroso compounds as a cause of human cancer. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific publication no 84. IARC, Lyon, pp 477–484

    Google Scholar 

  217. Preussmann R, Eisenbrand G (1984) N-Nitroso compounds in the environment. In: Searle CE (ed) Chemical carcinogens, 2nd edn, vol 2. American Chemical Society, Washington DC, Chap. 13 (ACS Monograph no 182).

    Google Scholar 

  218. Preussmann R, Stewart BW (1984) N-Nitroso carcinogens. In: Searle CE (ed) Chemical carcinogens, 2nd edn, vol 2. American Chemical Society, Washington DC, Chap. 12 (ACS Monograph no 182 ).

    Google Scholar 

  219. Preussmann R, Würtele G, Eisenbrand G, Spiegelhaider B (1978) Urinary excretion of N-nitrosodiethanolamine administered orally to rats. Cancer Lett 4: 207–209.

    PubMed  CAS  Google Scholar 

  220. Quintanilla M, Brown K, Ramsden M, Balmain A (1986) Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322: 78–80.

    PubMed  CAS  Google Scholar 

  221. Ramanathan R, Rajalakshmi S, Sarma DSR, Farber E (1976) Nonrandom nature of in vivo methylation by dimethylnitrosamine and subsequent removal of methylated products from rat liver chromatin DNA. Cancer Res 36: 2073–2079.

    PubMed  CAS  Google Scholar 

  222. Randerath K, Reddy MV, Disher RM (1986) Age-and tissue-related DNA modifications in untreated rats: detection by 32P-postlabelling assay and possible tumor induction and ageing. Carcinogenesis 7: 1615–1617.

    PubMed  CAS  Google Scholar 

  223. Reddy EP, Reynolds RK, Santos E, Barbacid M (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300: 149–152.

    PubMed  CAS  Google Scholar 

  224. Reddy MV, Gupta RC, Randerath E, Randerath K (1984) 32P-Postlabelling test for covalent DNA binding of chemicals in vivo: application to a variety of aromatic carcinogens and methylating agents. Carcinogenesis 5: 231–243.

    Google Scholar 

  225. Reiner B, Zamenhof S (1957) Studies on chemically reactive groups of DNA. J Biol Chem 228: 475–486.

    PubMed  CAS  Google Scholar 

  226. Renard A, Verly WG (1983) Repair of 06-ethylguanine DNA lesions in isolated cell nuclei: presence of activity in chromatin proteins. Eur J Biochem 136: 453–460.

    PubMed  CAS  Google Scholar 

  227. Reynolds SH, Stowers SJ, Patterson RM, Maronpot RR, Aaronson SA, Anderson MW (1987) Activated oncogenes in B6C3F1 mouse: implications for risk assessment. Science 237: 1309–1316.

    PubMed  CAS  Google Scholar 

  228. Rice JM, Ward JM (1982) Age dependence of susceptibility to carcinogenesis in the nervous system. Ann NY Acad Sci 381: 274–289.

    PubMed  CAS  Google Scholar 

  229. Rice S, Cheng MY, Cramer RE, Mandel M, Mower HF, Seff K (1984) Structure of N-methyl-N-pitro-N-nitrosoguanidine. J Am Chem Soc 106: 239–243.

    CAS  Google Scholar 

  230. Richardson KK, Richardson FC, Crosby RM, Swenberg JA, Skopek TR (1987) DNA base changes and alkylation following in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea. Proc Natl Acad Sci USA 84: 344–348.

    PubMed  CAS  Google Scholar 

  231. Roberts JJ (1978) Repair of DNA modified by cytotoxic mutagenic and carcinogenic chemicals. Adv Radiation Biol 7: 212–446.

    Google Scholar 

  232. Rodenhuis S, van de Wetering ML, Moot WJ, Evers SG, van Zandwijk N, Bos JL (1987) Mutational activation of the K-ras oncogene, a possible pathogenetic factor in adenocarcinoma of the lung. New England J Med 317: 929–935.

    CAS  Google Scholar 

  233. Roscoe JP, Claisse PJ (1976) Sequential in vivo-in vitro study of carcinogenesis induced in rat brain by ethylnitrosourea. Nature 262: 314–316.

    PubMed  CAS  Google Scholar 

  234. Rose FL (1958) Discussion to Magee PN: Some experimental studies on toxic liver injury. In: Walpole AL, Spinks A (eds) Symposium on evaluation of drug toxicity. J and A Churchill, London, p 116.

    Google Scholar 

  235. Ryan AJ, Billett MA, O’Connor PJ (1986) Selective repair of methylated purines in region of chromatin DNA. Carcinogenesis 7: 1497–1503.

    PubMed  CAS  Google Scholar 

  236. Saffhill R (1985) In vitro miscoding of alkylthymines with DNA and RNA polymerases. Chem Biol Interact 53: 121–130.

    PubMed  CAS  Google Scholar 

  237. Sandberg AA (1980) Chromosomes in human cancer and leukemia. Elsevier, New York Sander J (1968) Nitrosaminsynthese durch Bakterien. Z Physiol Chem 349: 429–432.

    Google Scholar 

  238. Sander J, Bürkle G (1969) Induktion maligner Tumoren bei Ratten durch gleichzeitige Verfütterung von Nitrit und sekundären Aminen. Z Krebsforschung 73: 54–66.

    CAS  Google Scholar 

  239. Saul RL, Kabir SH, Cohen Z, Bruce WR, Archer MC (1981) Re-evaluation of nitrate and nitrite levels in human intestine. Cancer Res 41: 2280–2283.

    PubMed  CAS  Google Scholar 

  240. Scherer E, Emmelot P (1975) Kinetics of evolution and growth of precancerous liver-cell foci and liver tumor formation by diethylnitrosamine in the rat. Eur J Cancer 11: 689–696.

    PubMed  CAS  Google Scholar 

  241. Schoental R, Rive DJ (1965) Interaction of JV-alkyl-N-nitrosourethanes with thiols. Biochem J 97: 466–474.

    PubMed  CAS  Google Scholar 

  242. Schräger TF, Busby WF, Goldman ME, Newberne PM (1986) Enhancement of methyl- benzyl-nitrosamine-induced esophageal carcinogenesis in zinc-deficient rats: effects on incorporation of [3H]thymidine into DNA of esophageal epithelium and liver. Carcinogenesis 7: 1121–1126.

    PubMed  Google Scholar 

  243. Schubert D, Heinemann S, Carlisle W, Tarikas H, Kimes B, Patrick J, Steinbach JH, Culp W, Brandt BL (1974) Clonal cell lines from the rat central nervous system. Nature 249: 224–227.

    PubMed  CAS  Google Scholar 

  244. Schulz U, McCalla DR (1969) Reactions of cysteine with N-methyl-N-nitroso-toluenesulphonamide and N-methyl-N-nitro-N-nitroso-guanidine. Can J Chem 47: 2021–2027.

    CAS  Google Scholar 

  245. Schwarz M, Appel KE, Schrenk D, Kunz W (1980) Effect of ethanol on microsomal metabolism of dimethylnitrosamine. J Cancer Res Clin Oncol 97: 233–240.

    PubMed  CAS  Google Scholar 

  246. Scribner JD, Ford GP (1982) Propyldiazonium ion alkylates 0-6 of guanine with rearrangement but alkylates N-7 without rearrangement. Cancer Letters 16: 51–56.

    PubMed  CAS  Google Scholar 

  247. Shibata M-A, Nakanishi K, Shibata M, Masui T, Miyata Y, Ito N (1986) Promoting effect of sodium chloride in two-stage urinary bladder carcinogenesis in rats initiated by N- butyl-N-(4-hydroxybutyl)nitrosamine. Urol Res 14: 201–206.

    PubMed  CAS  Google Scholar 

  248. Shih TY, Weeks MO (1984) Oncogenes and cancer. Cancer Invest 2: 109–123.

    PubMed  CAS  Google Scholar 

  249. Shirazi SS, Platz CE (1978) Effect of alcohol on canine oesophageal mucosa. J Surg Res 25: 373–379.

    PubMed  CAS  Google Scholar 

  250. Shuker DEG, Tannenbaum SR, Wishnok JS (1981) JV-Nitroso bile acid conjugates. I. Synthesis, chemical reactivity and mutagenic activity. J Org Chem 46: 2092–2096.

    Google Scholar 

  251. Shuker DEG, Bailey E, Parry A, Lamb J, Farmer PB (1987 a) Determination of urinary 3- methyladenine in humans as potential monitor of exposure to methylating agents. Carcinogenesis 8: 959–962.

    Google Scholar 

  252. Shuker DEG, Howell JR, Street BW ( 1987 b) Formation and fate of nucleic acid and protein adducts derived from N-nitroso-bile acid conjugates. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific publication no 84. IARC, Lyon, pp 187–193.

    Google Scholar 

  253. Sieber SM, Adamson RH (1979) Chemical carcinogenesis in non-human primates and attempts at prevention. In: Chandra P (ed) Antiviral mechanisms in the control of neoplasia. Plenum, New York, pp 455–479.

    Google Scholar 

  254. Singer B, Kusmierek J (1982) Chemical mutagenesis. Ann Rev Biochem 52: 655–693.

    Google Scholar 

  255. Singer B, Spengler SJ, Fraenkel-Corat H, Kusmierek JT (1986) 04-Methyl, -ethyl or -isopropyl substituents on thymidine in poly(dA-dT) all lead to transitions upon replication. Proc Natl Acad Sci USA 83: 28–32.

    Google Scholar 

  256. Singer GM, Lijinsky W, Buettner L, McClusky GA (1981) Relationship of rat urinary metabolites of N-nitrosomethyl-N-alkylamines to bladder carcinogenesis. Cancer Res 41: 4942–4946

    PubMed  CAS  Google Scholar 

  257. Solt D, Farber E (1976) New principle for analysis of chemical carcinogenesis. Nature 263: 701–703.

    CAS  Google Scholar 

  258. Spiegelhalder B, Preussmann R (1985) In vivo nitrosation of amidopyrine in humans: use of “ethanol effect” for biological monitoring of AT-nitrosodimethylamine in urine. Carcinogenesis 6: 545–548.

    PubMed  CAS  Google Scholar 

  259. Stewart BW, Swann PF, Holsman JW, Magee PN (1974) Cellular injury and car-cinogenesis. Evidence for alkylation of rat liver nucleic acids in vivo by N- nitrosomorpholine. Z Krebsforsch 82: 1–12.

    Google Scholar 

  260. Stewart M, Hill MJ, Pugh CRB, Williams JP (1981) Role of N-nitrosamines in carcinogenesis at the ureterocolic anastomosis. Br J Urol 53: 115–118.

    PubMed  CAS  Google Scholar 

  261. Stowers SJ, Wiseman RW, Ward JM, Miller EC, Miller J A, Anderson MW, Eva A (1988) Detection of activated proto-oncogenes in JV-nitrosodiethylamine-induced liver tumours: a comparison between B6C3FX mice and Fischer 344 rats. Carcinogenesis 9: 277–276

    Google Scholar 

  262. Strauss BS, Rabkin S, Sagher D, Moore P (1982) Role of DNA polymerase in base substitution mutagenesis on non-instructional templates. Biochimie 64: 829–838.

    PubMed  CAS  Google Scholar 

  263. Strauss BS, Larson K, Rabkin S, Sahm J, Shenkar R (1986) In vitro models for mutagenesis: a role for lesion, polymerase and sequence. Prog Clin Biol Res 209A: 149–159.

    Google Scholar 

  264. Suzuki E, Okada M (1980) Metabolic fate of N,N-dibutylnitrosamine in the rat. Gann 71: 863–870.

    PubMed  CAS  Google Scholar 

  265. Swann PF, Magee PN (1968) Nitrosamine-induced carcinogenesis. Alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J110: 39–47.

    CAS  Google Scholar 

  266. Swann PF, McLean AEM (1968) Effect of diet on the toxic and carcinogenic action of dimethylnitrosamine. Biochem J 107: 14–15.

    Google Scholar 

  267. Swann PF, Coe AM, Mace R (1984) Ethanol and dimethylnitrosamine and diethyl-nitrosamine metabolism and disposition in the rat. Possible relevance to the influence of ethanol on human cancer incidence. Carcinogenesis 5: 1337–1343.

    Google Scholar 

  268. Swenberg J A, Kerns WD, Mitchell RI, Caralla EJ, Pavkov KL (1980) Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure of formaldehyde vapor. Cancer Res 40: 3398–3402.

    PubMed  CAS  Google Scholar 

  269. Swenberg JA, Dyroff MC, Bedell MA, Popp J A, Huh N, Kirsten U, Rajewsky MF (1984) 04-Ethyldeoxythymidine but not 06-ethyldeoxyguanosine accumulates in hepatocyte DNA of rats continuously exposed to diethylnitrosamine. Proc Natl Acad Sci USA 81: 1692–1695.

    Google Scholar 

  270. Swenberg J A, Richardson FC, Tyeryar L, Deal F, Boucheron J (1987) Molecular dosimetry of DNA adducts formed by continuous exposure of rats to alkylating hepatocarcinogens. Prog Exp Tumor Res 31: 42–51.

    PubMed  CAS  Google Scholar 

  271. Swenson DH, Farmer PB, Lawley PD (1976) Identification of the methyl phosphotriester of thymidylyl(3,-5,)thymidine as a product from reaction of DNA with the carcinogen N-methyl-N-nitrosourea. Chem Biol Interact 15: 91–100.

    PubMed  CAS  Google Scholar 

  272. Swenson DH, Frei JV, Lawley PD (1979) Synthesis of l-(2-hydroxy)-l-nitrosourea and comparison of its carcinogenicity with that of 1-ethyl-1-nitrosourea. JNCI 63: 1469–1473

    Google Scholar 

  273. Swenson DH, Harbach PR, Trzos RT (1980) Relationship between alkylation of specific DNA bases and induction of sister chromatid exchange. Carcinogenesis 1: 931–936.

    PubMed  CAS  Google Scholar 

  274. Swenson DH, Petzold GL, Harbach PR (1986) Binding of l-(2-hydroxyethyl)-l- nitrosourea to DNA in vitro and to DNA of thymus and bone marrow in C57BL mice in vivo. Cancer Lett 33: 75–81.

    PubMed  CAS  Google Scholar 

  275. Tempest PR, Reeves BR, Spurr NK, Ranee AJ, Chan A M-L, Brookes P (1986) Activation of the met oncogene in the human MNNG-HOS cell line involves a chromosomal rearrangement. Carcinogenesis 7: 2051–2057.

    PubMed  CAS  Google Scholar 

  276. Terracini B, Testa MC, Cabral JR, Rossi L (1976) Roles of age at treatment and dose in carcinogenesis in C3Hf/Dp mice with a single administration of N-nitroso-N- methylurea. Br J Cancer 33: 427–439.

    Google Scholar 

  277. Thompson HJ, Meeker LD (1983) Induction of mammary gland carcinomas by subcutaneous injection of 1-methyl-1-nitrosourea. Cancer Res 43: 1628–1629.

    PubMed  CAS  Google Scholar 

  278. Thompson MH, Hill MJ (1987) Etiology and mechanism of carcinogenesis: diet, luminal factors and colorectal cancer. In: Faivre J, Hill MJ (eds) Causation and prevention of colorectal cancer. Elsevier, Amsterdam, pp 99–120.

    Google Scholar 

  279. Toksoz D, Farr CJ, Marshall CJ (1987) ras Gene activation in a minor proportion of the blast population in acute leukaemia. Oncogene 1: 409–413.

    Google Scholar 

  280. Topal MD, Eadie JS, Conrad M (1986) 06-Methylguanine mutation and repair is nonuniform. J Biol Chem 261: 9879–9885.

    Google Scholar 

  281. Umbenhauer D, Wild CP, Montesano R, Saffhill R, Boyle JM, Huh N, Kirstein V, Thomale J, Rajewsky MF, Lu SH (1985) 06-methyldeoxyguanonine in oesophageal DNA among persons at high risk from oesophageal cancer. Int J Cancer 36: 661–665.

    Google Scholar 

  282. Von Hofe E, Kleihues P, Keefer LK (1986) Extent of DNA 2-hydroxylation by N- nitrosomethylethylamine and N-nitrosodiethylamine in vivo. Carcinogenesis 7: 1335–1337

    Google Scholar 

  283. Von Hofe E, Schmerold I, Lijinsky W, Jeltsch P, Kleihues P (1987) DNA methylation in rat tissues by a series of homologous aliphatic nitrosamines ranging from N-nitroso- dimethylamine to N-nitrosomethyldodecylamine. Carcinogenesis 8: 1337–1341.

    Google Scholar 

  284. Wada S, Miyanishi M, Nishimato Y, Kambe S, Miller RW (1968) Mustard gas as a cause of respiratory neoplasia in man. Lancet 1: 1 161–1163.

    Google Scholar 

  285. Warren W (1984) Analysis of alkylated DNA by high pressure liquid chromatography. In: Venitt S, Parry JM (eds) Mutagenicity testing, a practical approach. IRL Press, Oxford, pp 25–44.

    Google Scholar 

  286. Warren W, Lawley PD (1980) Removal of alkylation products from DNA of Escherichia coli cells treated with carcinogens N-ethyl- and N-methyl-N-nitrosourea: influence of growth condition and DNA repair defects. Carcinogenesis 1: 67–78.

    CAS  Google Scholar 

  287. Warren W, Lawley PD, Gardner E, Harris G, Ball JK, Cooper CS (1987) Induction of thymomas by N-methyl-N-nitrosourea in ARK mice: interaction between chemical carcinogen and endogenous murine leukaemia viruses. Carcinogenesis 8: 163–172.

    PubMed  CAS  Google Scholar 

  288. Watson JD, Crick FHC (1953) Genetical implications of the structure of deoxyribose nucleic acids. Nature 171: 964–967.

    PubMed  CAS  Google Scholar 

  289. Waynforth HB, Magee PN (1975) Effects of various doses and schedules of administration of N-methyl-N-nitrosourea with and without croton oil promotion on skin papilloma production in BALB/c mice. Gann Monographs Cancer Res 17: 439–448.

    CAS  Google Scholar 

  290. White INH, Smith AG, Farmer PB (1983) Formation of N-alkylated protoporphyrin IX in livers of mice after diethylnitrosamine treatment. Biochem J 212: 599–608.

    PubMed  CAS  Google Scholar 

  291. Wild CP, Umbenhauer D, Chapot B, Montesano R (1986) Monitoring of individual human exposure to aflatoxins and N-nitrosamines by immunoassays. J Cell Biochem 30: 171–179.

    PubMed  CAS  Google Scholar 

  292. Wild CP, Lu SH, Montesano R (1987) Radioimmunoassay used to detect DNA alkylation adducts in tissues from populations at high risk from oesophageal and stomach cancer. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific vol no 84. IARC, Lyon, pp 534–537.

    Google Scholar 

  293. Williams GM (1987) Definition of a human cancer hazard. In: Butterworth BE, Slaga TJ (eds) Nongenotoxic mechanisms in carcinogenesis. Cold Spring Harbor Laboratory, New York, pp 367–380 (Banbury Report no 25 ).

    Google Scholar 

  294. Williams JC, Gusterson B, Humphreys J, Monaghan P, Coombes R, Rudland P, Neville AM (1981) N-Methyl-N-nitrosourea-induced rat mammary tumors. Hormone responsiveness but lack of spontaneous metastasis. JNCI 66: 147–151.

    Google Scholar 

  295. Williams LD, Shaw BR (1987) Protonated base pairs explain the ambiguous pairing properties of 06-methylguanine. Proc Natl Acad Sci USA 84: 1779–1783.

    PubMed  CAS  Google Scholar 

  296. Woodruff RC, Mason JM, Valencia R, Zimmering S (1984) Chemical mutagenesis testing in Drosophila. I. Comparison of positive and negative control data for sex-linked recessive lethal mutations and reciprocal translocations in three laboratories. Environ Mutagen 6: 189–202.

    Google Scholar 

  297. Yanez L, Groffen J, Valenzuela DM (1987) c-K-ras mutations in human carcinomas occur preferentially in codon 12. Oncogene 1: 315–318.

    Google Scholar 

  298. Yano K, Sonoda M, Sakagishi Y (1987) Reactions of N-nitrosoureas with cell membranes. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific vol no 84. IARC, Lyon, pp 202–205

    Google Scholar 

  299. Yarosh DB (1985) Role of 06-methylguanine-DNA methyltransferase in cell survival, mutagenesis and carcinogenesis. Mut Res 145: 1–16.

    CAS  Google Scholar 

  300. Yarosh DB, Fornace AJ, Day RS III (1985) Human 06-alkylguanine-DNA alkyltransferase fails to repair 04-methylthymine and methyl phosphotriesters in DNA as efficiently as does alkyltransferase from Escherichia coli. Carcinogenesis 7: 949–953.

    Google Scholar 

  301. Yoo J-S H, Ning SM, Patten CJ, Yang CS (1987) Metabolism and activation of N- nitrosodimethylamine by hamster and rat microsomes: comparative study with weanling and adult animals. Cancer Res 47: 992–998.

    PubMed  CAS  Google Scholar 

  302. Yu MC, Henderson BE (1987) Intake of Cantonese-style salted fish as a cause of nasopharyngeal carcinoma. In: Bartsch H, O’Neill IK, Schulte-Hermann R (eds) IARC scientific vol no 84. IARC, Lyon, pp 547–549.

    Google Scholar 

  303. Yunis J J, Soreng AL, Bowe AE (1987) Fragile sites are targets of diverse mutagens and carcinogens. Oncogene 1: 59–69.

    PubMed  CAS  Google Scholar 

  304. Zarbl H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M (1985) Direct mutagenesis of Ha-ras-1 oncogenes by N-methyl-N-nitrosourea during initiation of mammary carcinogenesis in rats. Nature 315: 382–385.

    PubMed  CAS  Google Scholar 

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Lawley, P.D. (1990). N-Nitroso Compounds. In: Cooper, C.S., Grover, P.L. (eds) Chemical Carcinogenesis and Mutagenesis I. Handbook of Experimental Pharmacology, vol 94 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74775-5_11

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