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Drug resistance and DNA repair

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Summary

DNA repair confers resistance to anticancer drugs which kill cells by reacting with DNA. A review of our current information on the topic will be presented here. Our understanding of the molecular biology of repair of 06-alkylguanine adducts in DNA has advanced as a result of the molecular cloning of the E. coli ada gene but the precise role of this lesion in the cytotoxic effects of alkylating agents in mammalian cells is not completely understood. Less progress has been made in understanding the enzymology and molecular biology of DNA cross-link repair even though such lesions are important for the cytotoxic effects of the widely used bifunctional alkylating agents and platinum compounds. It is evident that drug sensitive or resistant phenotypes are as highly complex as are the effects of DNA damage on cell metabolism and various aspects of these effects are discussed. Few clear correlations have been made between quantitative differences in DNA repair capacity and cellular sensitivity but assays which were developed to measure fidelity and intragenomic heterogeneity in DNA repair are beginning to be applied. Such studies may reveal subtle differences between sensitive and resistant cell lines. The molecular cloning of human DNA repair genes by transfection into drug sensitive rodent cells has been attempted. Some success has been achieved in this area but the functions of the cloned genes have yet to be identified.

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References

  1. Henderson JF: The experimental setting. In: Fox BW and Fox M (eds) Antitumour drug resistance. Springer Verlag: Berlin Heidelburg, New York, Tokyo, 1984. pp 23–35

    Google Scholar 

  2. Sager R, Gadi IK, Stephens L, Grabowy CT: Gene amplification: an example of accelerated evolution in tumourigenic mourigenic cells. Proc Nat Acad Sci (USA) 82: 7015–7019, 1985

    Google Scholar 

  3. Cifone MA, Fidler IJ: Increasing metastatic potential is associated with increasing genetic instability of clones isolated from murine neoplasms. Proc Nat Acad Sci (USA) 78: 6949–6952, 1981

    Google Scholar 

  4. Kerbal RS, Davies AJS: Facilitation of tumour progression by cancer therapy. Lancet 30: 977–978, 1982

    Google Scholar 

  5. Fox BW, Fox M (eds) Antitumour drug resistance. Springer Verlag: Berlin Heidelburg, New York, Tokyo, 1984

    Google Scholar 

  6. Jones AP: Altering gene expression with 5-azacytidine. Cell 40: 485–486, 1985

    Google Scholar 

  7. Jones PA: DNA methylation and cancer. Cancer Res 46: 461–466, 1986

    Google Scholar 

  8. Wilson VL, Jones PA: Inhibition of DNA methylation by chemical carcinogens in vitro. Cell 32: 239–246, 1984

    Google Scholar 

  9. Sartorelli AC: Malignant cell differentiation as a potential therapeutic approach. Brit J Cancer 52: 293–302, 1985

    Google Scholar 

  10. Stephans TC, Adams K, Peacock JH: Emergence of nitrosourea resistant sublines of Lewis lung tumor following MeCCNU treatment in vivo. Brit J Cancer 53: 237–245, 1986

    Google Scholar 

  11. Goldie JH, Goldman AJ, Gudauskas GA: Rationale for the use of alternating non-cross-resistant chemotherapy. Cancer Treatment Repts 66: 439–449, 1982

    Google Scholar 

  12. Shimke RT, Sherwood SW, Hill AB, Johnson RN: Over-replication and recombination of DNA in higher eukaryotes: Potential consequences and biological implications. Proc Natl Acad Sci (USA) 83: 2157–2161, 1986

    Google Scholar 

  13. Johnson NP, Hoeschele JD, Rahn RO, O'Neill JP, Hsie AW: Mutagenicity cytotoxicity and DNA binding of Platinum (11)-chloroammines in Chincse hamster ovary cells. Cancer Res 40: 1463–1468, 1980

    Google Scholar 

  14. Singh B, Gupta RS: Mutagenic responses of thirteen anti-cancer drugs on mutation induction at multiple genetic loci and on sister chromatid exchanges in Chinese hamster ovary cells. Cancer Res 43: 577–584, 1983

    Google Scholar 

  15. Thacker J: The molecular nature of mutations in cultured mammalian cells: A review. Mut Res 150: 431–442, 1985

    Google Scholar 

  16. Fox M: Drug resistance and DNA repair. In: Fox BW, Fox M (eds) Antitumour drug Resistance. Springer Verlag: Berlin, Heidelburg, New York, Tokyo, 1984, pp 335–362

    Google Scholar 

  17. Friedberg EC, Hanawalt PC (eds). DNA repair: A Laboratory Manual of Research Procedures, Vol 1 Pts A & B. Marcel Decker Inc., New York, Basel, 1981

    Google Scholar 

  18. Mulligan RC, Berg P: Expression of a bacterial gene in mammalian cells. Science 209: 1422–1427, 1980

    Google Scholar 

  19. Thacker J: The use of recombinant DNA techniques to study radiation induced damage repair and genetic change in mammalian cells. Int J Rad Biol 50: 1–31, 1986

    Google Scholar 

  20. Cox R, Masson WK, Debenham PG, Webb MBT: The use of recombinant DNA plasmids for the determination of DNa-repair and recombination in cultured mammalian cells. Brit J Cancer 9: Suppl VI 67–72, 1984

    Google Scholar 

  21. Jaspers NG, Painter RB, Paterson MC, Kidson C, Inoue T: Complementation analysis of ataxia telangiectasia. KROC Found. Ser 9: 147–162, 1985

    Google Scholar 

  22. Knox RJ, Lydall DA, Friedlos F, Basham C, Roberts JJ: The effect of monofunctional or difunctional platinum adducts and of various other DNA damage on the expression of transfected DNA in mammalian cell lines inherently sensitive or resistant to difunctional agents. Biochem Biophys Acta 908: 214–223, 1987

    Google Scholar 

  23. Jeggo PA, Kemp LM: X ray sensitive mutants of a Chinese hamster ovary cell line: isolation and cross sensitivity to DNA damaging agents. Mut Res 112: 313–319, 1983

    Google Scholar 

  24. Thompson LH, Rubin JS, Cleaver JE, Whitmore GF, Brokman K: A screening method for isolating DNA repair deficient mutants of CHO cells. Somatic Cell Genet 6: 391–406, 1980

    Google Scholar 

  25. Jones NJ, Debenham PG, Thacker J: New X ray sensitive mutants of cultured hamster cells. A Brit J Cancer 54: 349, 1986

    Google Scholar 

  26. Jeggo PA, Holliday R: Azacytidine-induced reactivation of a DNA repair gene in Chinese hamster ovary cells. Mol and Cell Biol 6: 2944–2949, 1986

    Google Scholar 

  27. Olsson M, Lindahl T: Repair of alykylated DNA in E. coli: methyl group transfer from 06methylguanine to a protein cysteine residue. J Biol Chem 255: 10369–10571, 1980

    Google Scholar 

  28. Morimoto K, Dolan ME, Scichitano D, Pegg AE: Repair of 06propylguanine and 06butylguanine in DNA by 06-alkylguanine DNA alkyltransferases from rat liver and E. coli. Carcinogenesis 6: 1027–1031, 1985

    Google Scholar 

  29. Sedgwick B: Molecular cloning of a gene which regulates the adaptive response to alkylating agents in E. coli. Mol and Gen Genet 191: 466–472, 1983

    Google Scholar 

  30. Margison GP, Cooper DP, Brennand J: Cloning of the E. coli 06methylguanine and methylphosphotriester methyltransferase gene using a functional DNA repair assay. Nucleic Acids Res 13: 1939–1952, 1984

    Google Scholar 

  31. Nakabeppu Y, Kondo H, Kawabata S, Iwanaga S, Sekiguichi M: Purification and structure of the intact ada regulatory protein E. coli K12 06methylguanine DNA methyltransferase. J Biol Chem 260: 7281–7288, 1985

    Google Scholar 

  32. Demple B, Sedgwick B, Robins P, Totty N, Waterfield MP, Lindahl T: Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. Proc Nat Acad Sci USA 82: 2688–2692, 1985

    Google Scholar 

  33. Teo I, Sedgwick G, Demple B, Li B, Lindahl T: Induction of resistance of alkylating agents in E. coli: the ada+ gene product serves both as a regulatory protein and as an enzyme for repair of mutagenic damage. EMBO J 3: 2151–2157, 1983

    Google Scholar 

  34. Brent TP: Inactivation of purified human 06alkylguanine alkyltransferase by alkylating agents or alkylated DNA. Cancer Res 46: 2320–2323, 1986

    Google Scholar 

  35. Yarosh DB, Barnes D, Erickson LC: Transfection of DNA from a chloroethylnitrosourea-resistant tumour cell line (mer+) to a sensitive cell line (mer+) results in a tumour cell line resistant to MNNG and CNU has increased 06-methylguanine DNA methyltransferase levels and reduced levels of DNa cross-linking. Carcinogenesis 7: 1603–1606, 1986

    Google Scholar 

  36. Saffhill R, Margison GP, O'Connor PJ: Mechanisms of carcinogenesis induced by alkylating agents. Biochem Biophys Acta 823: 111–145, 1985

    Google Scholar 

  37. Warren W, Crathorn AR, Shooter KV: The stability of methylated purines and of methylphosphotriesters in DNA of V79 cells after treatment with N-methyl-N-nitrosourea. Biochem Biophys Acta 563: 82–88, 1979

    Google Scholar 

  38. Goth-Goldstein R: Inability of Chinese hamster ovary cells to excise 06alkylguanine. Cancer Res 40: 2633–2624, 1980

    Google Scholar 

  39. Day RS, Ziolkowski CHJ: Human brain tumour cell strains with deficient host cell reactivation of N-methyl N-nitro-N-nitrosoguanidine damaged adenovirus 5. Nature (London) 279: 797–799, 1977

    Google Scholar 

  40. Yarosh DB: The role of 06methylguanine DNA methyltransferase in cell survival mutagenesis and carcinogenesis. Mut Res 145: 1–16, 1985

    Google Scholar 

  41. Brennand J, Margison GP: Expression of the E. coli 06methylguanine methylphosphotriester gene in mammalian cells. Carcinogenesis 7: 185–188, 1986

    Google Scholar 

  42. Margison GP, Brennand J: Reduction of the toxicity and mutagenicity of alkylating agents in mammalian cells harbouring the E. coli alkyltransferase gene. Proc Nat Acad Sci 83: 6292–6296, 1986

    Google Scholar 

  43. Roberts JJ: The repair of DNA modified by cytotoxic mutagenic and carcinogenic chemicals. Advances in Rad Biol 7: 211–381, 1978

    Google Scholar 

  44. Baker RM, vanVoorhis WC, Spencer IA: HeLa cell variants that differ in sensitivity to monofunctional alkylating agents with independence of cytotoxic and mutagenic responses. Proc Nat Acad Sci (USA) 76: 5249–5253, 1979

    Google Scholar 

  45. Ockey CH, Brennand J, Margison GP: The frequency of N-methyl-N-nitrosourea induced sister chromatid exchanges is reduced in mammalian cells expressing the E. coli 06guanine alkyltransferase gene. Brit J Cancer 54: 366, 1986

    Google Scholar 

  46. Shaffer DA: Replication bypass model of sister chromatid exchanges and implications for Bloom's syndrome and Fanconi's anaemia. Human Genetics 37: 177–190, 1977

    Google Scholar 

  47. Sutter W, Brennand J, McMillan S, Fox M: Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells; independence of cytotoxic and mutagenic responses. Mut Res 73: 171–181, 1980

    Google Scholar 

  48. Karran P, Lindahl T: Cellular defence mechanisms against alkylating agents. Cancer Surveys 4: 583–595, 1985

    Google Scholar 

  49. Durrant LG, Margison GP, Boyle JM: Pretreatment of Chinese hamster V79 cells with MNU increases survival without affecting DNA repair or mutagenicity. Carcinogenesis 2: 55–60, 1981

    Google Scholar 

  50. Karran P, Williams SA: The cytotoxic and mutagenic effects of alkylating agents on human lymphoid cells are caused by different DNA lesions. Carcinogenesis 6: 789–792, 1985

    Google Scholar 

  51. Holliday R, Jeggo PA: Mechanisms for changing gene expression and their possible relationship to carcinogenesis. Cancer Surveys 4: 557–581, 1985

    Google Scholar 

  52. Laval F: Inducible repair of alkylation damage in mammalian cells. Proc Natl Acad Sci (USA) 81: 1962–1966, 1984

    Google Scholar 

  53. Laval F, Laval J: Adaptive response in mammalian cells: Cross reactivity of different pre-treatments on cytotoxicity as contrasted to mutagenicity. Proc Natl Acad Sci (USA) 81: 1062–1066, 1984

    Google Scholar 

  54. Boyle JM, Saffhill R, Margison GP, Fox M: A comparison of cell survival mutation and persistance of putative promutagenic lesions in Chinese hamster cells exposed to BNU or MNU. Carcinogenesis 1981–1985, 1986

  55. Boyle JM, GP Margison, Saffhill R: Evidence for excision repair of 06nButyldeoxyguanosine in human cells. Carcinogenesis 1987–1990, 1986

  56. Erickson LC, Bradley MO, Kohn KW: Measurements of DNA damage in Chinese hamster cells treated with equitoxic and equimutagenic doses of nitrosoureas. Cancer Res 38: 3379–3384, 1978

    Google Scholar 

  57. Erickson LC, Laurent G, Sharkey NA, Kohn KW: DNA cross-linking and monoadduct repair in nitrosourea-treated human tumour cells. Nature 288: 727–729, 1980

    Google Scholar 

  58. Bodell WJ, Aida T, Berger MS, Rosenblum ML: Increased repair of 06alkylguanine adducts in glioma derived human cells resistant to the cytotoxic and cytogenetic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea. Carcinogenesis 7: 879–883, 1986

    Google Scholar 

  59. Bodell WJ, Aida T, Berger MS, Rosenblum ML: Repair of 06-(2-chloroethyl)guanine mediates the biological effects of chloroethylnitrosoureas. Environ Health Persp 62: 119–126, 1985

    Google Scholar 

  60. Day RS, Ziolkowski CJH, Scudiero DA, Myer SA, Lubiniecki AS, Giradi AJ, Galloway SM, Bynum CD: Defective repair of alkylated DNA by human tumour and SV40 transformed human cell strains. Nature 288: 724–727, 1980

    Google Scholar 

  61. Fox M, Scott D: The genetic toxicology of nitrogen and sulphur mustard. Mut Res 75: 131–168, 1980

    Google Scholar 

  62. Fox BW: Alkylating agents: Mechanisms of Resistance. A Review. 13th Int. Cancer Congress PtC Biology of Cancer (2). Alan R Liss, Inc. 1983 p 247–255

  63. Dean SW, Fox M: DNA repair, DNA synthesis and cell cycle delay in human lymphoblastoid cells differentially sensitive to nitrogen mustard. Mut Res 132: 63–72, 1984

    Google Scholar 

  64. Dean SW, Fox M: Investigation of the cell cycle response of normal and Fanconi anaemia fibroblasts to nitrogen mustard using flow cytometry. J Cell Science 64: 265–279, 1983

    Google Scholar 

  65. Dean SW, Johnson AB, Tew KD: A comparative analysis of drug induced DNA effects in a nitrogen mustard resistant cell line expressing sensitivity to nitrosoureas. Biochemical Pharmacol 35: 1171–1176, 1986

    Google Scholar 

  66. Prestayko AW, Crooke ST, Carter SK (eds) Cisplatin current status and new developments. Academic Press, New York, 1980

    Google Scholar 

  67. Pascoe JM, Roberts JJ: Interactions between mammalian cell DNA and inorganic platinum compounds. I. DNA interstrand crosslinking and cytotoxic properties of platinum II compounds. Biochemical Pharmacol 23: 1345, 1974

    Google Scholar 

  68. Plooy ACM, vanDijk M, Lohman PHM: Induction and repair of DNA crosslinks in Chinese hamster ovary cells treated with various platinum compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity and antitumour activity. Cancer Res 44: 2043–2051, 1984

    Google Scholar 

  69. Zwelling LA, Anderson T, Kohn KW: DNA-protein and DNA interstrand crosslinking by cis- and trans-platinum (II) diamminedichloride in L1210 mouse leukemia cells and in relation to cytotoxicity. Cancer Res 39: 365–369, 1979

    Google Scholar 

  70. Bergerat J-P, Drewinko B, Corry P, Barlogic B, Ho DH: Synergistic lethal effects of cis-dichlorodiammineplatinum and 1-D-arabinofuranosylcytosine. Cancer Res 41: 25–30, 1981

    Google Scholar 

  71. Meyn RE, Corry PM, Fletcher SE, Demetriades M: Thermal enhancement of DNA damage in mammalian cells treated with cis-diamminedichloroplatinum (II). Cancer Res 40: 1136–1139, 1980

    Google Scholar 

  72. Pinto AL, Lippard SJ: Binding of the antitumor drug cis-diamminedichloroplatinum (II) (Cisplatin) to DNA. Biochem Biophys Acta 780: 167–180, 1985

    Google Scholar 

  73. Tullius TD, Lippard SJ: Cis-Diamminedichloroplatinum (II) binds in a unique manner to oligo(dG)-oligo(dC) sequence in DNA — a new assay using Exonuclease III. J Am Chem Soc 103: 4620, 1981

    Google Scholar 

  74. Royer-Pokora B, Gordon LK, Haseltine WA: Use of exonuclease III to determine the site of stable lesions in defined sequences of DNA: the cyclobutane pyrimidine dimer and cis and trans-dichlorodiammineplatinum II examples. Nucleic Acid Res 9: 4595–4609, 1981

    Google Scholar 

  75. Drobnik J, Urbankova MM, Krekulova A: The effect of cis dichlorodiammineplatinum (II) on Escherichia coli B. Mutation Res 17: 13–20, 1973

    Google Scholar 

  76. Beck DJ, Brubaker RR: Effect of cis-platinum (II)diammine dichloride on wild type and deoxyribonucleic acid repair-deficient mutants of Escherichia coli. J Bact 116: 1247, 1973

    Google Scholar 

  77. Beck DJ, Popoff S, Sancar A, Rupp D: Reactions of the UVRABC excision nuclease with DNA damaged by diamminedichloroplatinum (II). Nucleic Acids Res 13: 7395–7412, 1985

    Google Scholar 

  78. Van denBerg HW, Roberts JJ: Investigations into the mechanism of action of anti-tumour platinum compounds: time- and dose-dependent changes in the alkaline sucrose gradient sedimentation profiles of DNA from hamster cells treated with cis-platinum (II)diamminedichloride. Chem-Biol Interactions 11: 493–499, 1975

    Google Scholar 

  79. Pera Jr MF, Rawlings CJ, Shackleton J, Roberts JJ: Quantitative aspects of the formation and loss of DNA interstrand crosslinks in Chinese hamster cells following treatment with cis-diamminedichloroplatinum (II). II. Comparison of results from alkaline clution, DNA renaturation and DNA sedimentation. Biochem Biophys Acta 655: 152, 1981

    Google Scholar 

  80. Fraval HNA, Roberts JJ: Excision repair of cis-diamminedichloroplatinum (II)-induced damage to DNA in Chinese hamster cells. Cancer Res 39: 1793–1797, 1979

    Google Scholar 

  81. Ciccarelli RB, Solomon KJ, Varshavsky A, Lippard SJ: In vivo effects of cis- and trans-diamminedichloroplatinum (II) on SV40 chromosomes: Differential repair, DNA-protein crosslinking, and inhibition of replication. Biochemistry 24: 7533–7540, 1985

    Google Scholar 

  82. Roberts JJ, Friedlos F: The differential toxicity of cis- and trans-diamminedichloroplatinum (II) towards mammalian cells lack of influence of any difference in the rates of loss of their DNA-bound adducts. Cancer Res 47: 31–36, 1987

    Google Scholar 

  83. Fraval HNA, Rawlings CJ, Roberts JJ: Increased sensitivity of UV-repair deficient human cells to DNA bound platinum products which unlike thymine dimers are not recognized by an endonuclease extracted from M. Luteus. Mutation Res 51: 121–132, 1978

    Google Scholar 

  84. Rawlings CJ, Roberts JJ: Walker rat carcinoma cells are exceptionally sensitive to cis-diamminedichloroplatinum (II) (Cisplatin) and other difunctional agents but not defective in the removal of platinum DNA adducts. Mutation Res 166: 157–168, 1986

    Google Scholar 

  85. Strandberg MC, Bresnick E, Eastman A: The significance of DNA cross-linking to cis-diamminedichloroplatinum (II)-induced cytotoxicity in sensitive and resistant lines of murine leukemia L1210 cells. Chem-Biol Interactions 39: 169–180, 1982

    Google Scholar 

  86. Micetich K, Zwelling LA, Kohn KW: Quenching of DNA: Platinum (II) monoadducts as a possible mechanism of resistance to cis-diamminedichloroplatinum (II) in L1210 cells. Cancer Res 43: 3609–3613, 1983

    Google Scholar 

  87. Roberts II, Friedlos F, Scott D, Ormerod MG, Rawlings CJ: The unique sensitivity of Walker rat tumour cells to difunctional agents is associated with a failure to recover from inhibition of DNA synthesis, and increased chromosome damage. Mutation Res 166: 169–181, 1986

    Google Scholar 

  88. Hoy CA, Thompson LH, Salazar EP, Stewart SA: Different genetic alterations underlie dual hypersensitivity of CHO mutant UV-1 to DNA methylating and cross linking agents. Somatic Cell Mol Genetics 11: 523–532, 1985

    Google Scholar 

  89. Robson CN, Harris AL, Hickson LD: Isolation and characterisation of Chinese hamster ovary cell lines sensitive to mitomycin C and bleomycin. Cancer Res 45: 5304–5309, 1985

    Google Scholar 

  90. Fox M, Bloomfield ME, Hopkins J, Boyle JM: Differential responses of nascent DNA synthesis and chain elongation in V79 and V79/79 cells exposed to UV light and chemical mutagens. Carcinogenesis 4: 261–268, 1983

    Google Scholar 

  91. Graham A, Fox M: The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage. Carcinogenesis 4: 269–274, 1983

    Google Scholar 

  92. Bush DB, Cleaver JE, Glaser DA: Large scale isolation of UV sensitive clones of CHO cells. Somatic Cell Genetics 6: 407–418, 1980

    Google Scholar 

  93. Thompson LH, Bush DB, Brookman K, Mooney CL, Glaser DA: Genetic diversity of ultraviolet sensitive DNA repair mutants of Chinese hamster ovary cells. Proc Natl Acad Sci (USA) 78: 3734–3737, 1981

    Google Scholar 

  94. Friedberg EC: Nucleotide excision repair of DNA in cukaryotes: comparisons between human cells and yeast. Cancer Surveys 4: 529–555, 1985

    Google Scholar 

  95. Westerveld A, Hocijmakers AJ, vanDuin M, Odijk H, Wood RD, Bootsma D: Molecular cloning of a human DNA repair gene. Nature (London) 310: 425–429, 1984

    Google Scholar 

  96. MacInnes MA, Bingham JM, Thompson LH, Strniste GF: DNA mediated cotransfer of excision repair capacity and drug resistance into Chinese hamster ovary mutant cell line UV 135. Mol and Cell Biol 4: 1152–1158

  97. Rubin JS, Prideaux VR, Huntington HF, Dulhanty AM, Whitmore GF, Bernstein A: Molecular cloning and chromosomal mosomal location of DNA sequences associated with a human DNA repair gene. Mol and Cell Biol 5: 398–405, 1985

    Google Scholar 

  98. Mullenders LHF, vanKesteren AC, Bussmann CUM, vanZeeland AA, Natarajan AT: Distribution of UV induced repair events in higher order chromatin loops in human and hamster fibroblasts. Carcinogenesis 7: 995–1002, 1986

    Google Scholar 

  99. Mullenders LHF, vanKesteren AC, Bussmann GJM, vanZeeland AA, Natarajan AT: Preferential repair of nuclear matrix associated DNA in xeroderma pigmentosum group C. Mut Res 141: 75–82, 1984

    Google Scholar 

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

    Google Scholar 

  101. Bohr VA, Smith CA, Okumoto DS, Hanawalt PC: DNA repair in active genes: removal of pyrimidine dimers from the DHFR gene in CHO cells is much more efficient than in the genome overall. Cell 40: 359–369, 1985

    Google Scholar 

  102. Madhani HD, Bohr VA, Hanawalt PC: Differential repair in transcriptionally active and inactive proto-oncogenes c abl and c mos. Cell 45: 417–423, 1986

    Google Scholar 

  103. Mattler WB, Hartley JA, Rahn RO, Gibson N, Kohn KW: Sequence specificity of DNA alkylating agents and their preferential binding to Ha-ras sequences. Abstract Int. Conf. on mechanisms of DNA damage and repair. Implications for carcinogenesis and risk assessment. Gaithersburg, Maryland U.S.A., June, 1985

  104. Furois-Corbin S, Pullman B: Specificity of carcinogen DNA interaction: A thcoretical exploration of the factors involved in the effect of neighbouring bases on N-methyl N-nitrosourea alkylation of DNA. Chem Biol Int 54: 9–13, 1985

    Google Scholar 

  105. Briscoe WT, Cotter LE: DNA sequence has an effect on the extent and kinds of alkylation of DNA by a potent carcinogen. Chem Biol Int 56: 321–331, 1985

    Google Scholar 

  106. Boitcaux S, Costade Oliveira R, Laval J: The Escherichia coli 06 methyltransferase does not repair promutagenic 05 methylguanine residues when present in Z DNA. J Biol Chem 206: 8711–8715, 1985

    Google Scholar 

  107. Newman CN, Miller JH: Mechanism of UV induced deoxynucleoside triphosphate pool imbalance in CHO-K1 cells. Mutation Res 145: 95–101, 1985

    Google Scholar 

  108. Kunz BA: Genetic effects of deoxyribonucleotide pool imbalances. Environmental Mut 4: 695–727, 1982

    Google Scholar 

  109. Fox M: The effects of pyrimidine nucleotides on alkylating agent induced cytotoxicity and spontaneous and induced mutation to purine analogue resistance in V79 cells. In: FJ de Serres (ed) Genetic Consequences of nucleotide pool imbalance. Plenum 1985, pp 435–440

  110. Weinburg GL, Ullman B, Wright CM, Martin DW: The effects of exogenous thymidine on endogenous deoxynucleotides and mutagenesis in mammalian cells. Somatic Cell and Mol Genetics 11: 413–419, 1985

    Google Scholar 

  111. Kameshita I, Matsuda Z, Taniguchi T, Shizuta Y: Poly (ADP ribose) synthetase. J Biol Chem 259: 4770–4776, 1984

    Google Scholar 

  112. Kreimeyer A, Wieckens K, Adametz P, Hilz H: DNA repair-associated ADP ribosylation in vivo. J Biol Chem 259: 890–896, 1984

    Google Scholar 

  113. Boechun TLJ, Drahovsky D: Hypomethylation of DNA in Raji cells after treatment with N-methyl-N-nitrosourea. Carcinogenesis 2: 39–42, 1981

    Google Scholar 

  114. Tisdale MJ: Antitumour imidazotetrazines X effect of 8-carbomyl-3-methylimidozo [5–1-d] 1235 tetrazin-4 (3H) one (CCRG 81045 M & B 39831 NSC 362856) on DNA methylation during induction of haemoglobin synthesis in human leukemia cell line K562. Biochem Pharmacol 35: 311–316, 1986

    Google Scholar 

  115. Nyce J, Liu L, Jones PA: Variable effects of DNA synthesis inhibitors upon DNA methylation in mammalian cells. Nucl Acid Res 14: 4353–4367, 1986

    Google Scholar 

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  1. Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, M20 9BX, Manchester, UK

    Margaret Fox

  2. Institute of Cancer Research, Royal Cancer Hospital, Clifton Avenue, SM2 5PX, Sutton, Surrey, UK

    John J. Roberts

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Fox, M., Roberts, J.J. Drug resistance and DNA repair. Cancer Metast Rev 6, 261–281 (1987). https://doi.org/10.1007/BF00144267

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