Abstract
The aim of this pilot was to evaluate the feasibility of incorporating several complementary biologic markers into a molecular epidemiologic study of chemotherapy patients. Thirty-two cancer patients being treated withcis-DDP-based chemotherapy for the first time were enrolled in the study and donated a baseline sample and at least one post-treatment sample of blood. Sister Chromatid Exchange (SCEs) and plasma protein and hemoglobin binding bycisDDP were significantly increased in samples drawn at various timepoints following treatment. The pattern of nine different oncogene protein products (including those ofras, fes, andmyc) remained unchanged in sera of six patients followed over the course of their treatment. However, the levels ofras P21 product were significantly elevated above normal, control levels in all six cancer patients — both prior to and throughout the course of chemotherapy. These results suggest the usefulness of utilizing a battery of markers to evaluate biologic response to cisplatinum-based chemotherapy.
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References
Balmain A, Pragneil IB (1983) Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming harvey-ras oncogene. Nature 303: 72–74
Brandt-Rauf PW, Niman HL (1988) Serum screening for oncogene proteins in workers exposed to PCBs. Br J Ind Med 45: 689–693
Carrano AV, Moore DH (1982) The rationale and methodology for quantifying sister chromatid exchange in humans. In: Heddle JA (ed) Mutagenicity: new horizons in genetic toxicology. Academic Press, New York, pp 267–304
de Serres FJ, Matsushima T (1988) Meeting report; approaches for human population monitoring. Mutat Res 203: 185–195
Eastman A (1984) Characterization of the interaction ofcis-dichloroethylenediammine platinum (II) with the DNA of sensitive and resistant L1210 cells. Proc Am Assoc Cancer Res 25: 367 (abstr.)
Einhorn LH, Donohue J (1977)Cis-Diamminedichloroplatinum, vinblastine, and bleomycin chemotherapy in disseminated testicular cancer. Ann Intern Med 87: 293–298
Fichtinger-Schepman AMJ, Van Oosterom AT, Lohman PHM, Berends F (1987)Cis-Diamminedichloroplatinum (II)-induced DNA adducts in peripheral leukocytes from seven cancer patients: quantitative immunochemical detection of the assuct induction and removal after a single dose of cis-Diamminedichloroplatinum (II). Cancer Res 47: 3000–3004
Filipski J, Kohn KW, Prather R, Bonner WM (1979) Thiourea reverses cross-links and restores biological activity in DNA treated with dichlorodiamino-platinum (II). Science 204: 181–183
Johnson DC, Leudke DW, Sapiente RA, Naidu RB (1980) Acute lymphocytic leukemia in a male with germ cell carcinoma. A case report. Med Pediatr Oncol 8: 361–365
Kurzrock R, Gallick GE, Gutterman JU (1986) Differential expression of p21 ras gene products among histological subtypes of fresh primary human lung tumors. Cancer Res 46: 1530–1534
Leopold WR, Miller EC, Miller JA (1979) Carcinogenicity of antitumorcis-platinum (II) coordination complexes in the mouse and rat. Cancer Res 39: 913–918
Marshall CJ, Voosden KH, Phillips DH (1984) Activation of c-Ha-ras-1 proto-oncogene by in vitro modification with a chemical carcinogen, benzo(a)pyrene diol epoxide. Nature 310: 586–589
Mead GM, Green JA, Macbeth FR, Williams CJ, Whitehouse JMA, Buchanan R (1983) Second malignancy after cisplatin, vinblastine and bleomycin (PVB) chemotherapy: a case report. Cancer Treat Rep 67: 410
Mustonen R, Hemminki K, Alhonen A, Hietanen P, Kiilunen M (1988) Determination ofcis-diamminedichloroplatinum (II) in blood compartments of cancer patients. In: Bartsch H. Hemminki K. O'Neill IK (eds) Methods for detecting DNA damaging agents in man: application in cancer epidemiology and prevention. International Agency for Research on Cancer, Lyon
Mustonen R, Takala M, Leppala S, Hemminki K (1989) Dose-dependence and stability of cisplatin binding to tissue DNA and blood proteins in rats. Carcinogenesis 10: 365–368
Mustonen R, Hietanen P. Leppala S, Takala M, Hemminki K (1990) Determination ofcis-diamminedichloroplatinum (II) in plasma proteins and hemoglobin of cancer patients. Arch Toxicol (in press)
Niman HL, Thompson AMH, Yu A, Markham M, Willems JJ, Herwig KR, Habib NA, Wood CB, Houghten RA, Lerner RA (1985) Antipeptide antibodies detect oncogene-related proteins in urine. Proc Natl Acad Sci USA 82: 7924–7928
Reed E, Yuspa S, Zwelling LA, Ozols RF, Poirier MC (1986) Quantitation ofcis-diamminedichloroplatinum (II) (cisplatin)-DNA-intrastrand adducts in testicular and ovarian cancer patients receiving cisplatin chemotherapy. J Clin Invest 77: 545–550
Sherman SE, Gibson D, Wang AH-J, Lippard SJ (1985) X-ray structure of the major adduct of the anticancer drug cisplatin with DNA. Science 230: 412–417
Singh B, Gupta RS (1983) Mutagenic response of thirteen anti-cancer drugs on mutation induction at multiple genetic loci and on sister chromatid exchanges in Chinese hampter ovary cells. Cancer Res 43: 577–584
Sklar MD (1988) Increased resistance to cis-diamminedichloroplatinum (II) in NIH 3T3 cells transformed by ras oncogenes. Cancer Res 48: 793–797
Slamon DJ, de Kernian JB, Verma IM, Cline MJ (1984) Expression of celllular oncogenes in human malignancies. Science 224: 256–262
Sukumar S, Pulciani S, Doniger J. DiPaolo JA, Evans CH, Zbar B, Barbacid M (1984) A transforming ras gene in tumorigenic guinea pig cell lines initiated by diverse chemical carcinogens. Science 223: 1197–1199
Terheggen PMAB, Dijkman R, Begg AC, Dubbelman R, Floot BGJ, Hart AAM, den Engelse L (1988) Monitoring of interaction products ofcis-diamminedichloroplatinum(II) andcis-diammine (1, 1-cyclobutanedicarboxylato) platinum (II) with DNA in cells from platinum-treated cancer patients. Cancer Res 48: 5597–5603
Tominaga K, Shinkai T, Saijo N, Eguchi K, Shimizu E, Sasaki Y, Fujita J, Nakajima T (1984) Sister chromatid exchanges induced in human lymphocytes by cis-diamminedichloroplatinum(II). Jpn J Clin Oncol 14: 659–665
Tominaga K, Shinkai T, Saijo N, Nakajima T, Ochi H, Suemasu K (1986) Cytogenetic effects of etoposide V-16 on human lymphocites, with special reference to the relation between sister chromatid exchange and chromatid breakage. Jpn J Cancer Res 77: 385–391
Van Imhoff GW, Sleijfer D, Breuning MH, Anders G, Mulder NH, Halie MR (1986) Acute nonlymphocytic leukemia 5 years after treatment with cisplatin, vinblastine and bleomycin for disseminated testicular cancer. Cancer 57: 984–987
Vermoken JB, van der Vijgh WJF, Klein I, Gall HE, van Groeningen CJ, Hart GAM, Pinedo HM (1986) Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin. Clin Pharmacol Ther 39: 136–144
Wiencke JK, Cervenka J, Kennedy BJ, Prlina J, Gorlin R (1982) Sisterchromatid exchange induction bycis-platinum/adriamycin cancer chemotherapy. Mutat Res 104: 131–136
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This work was supported in part by the Columbia Cancer Center and by PHS grants CA 47351 and OH 00076
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Perera, F., Fischman, H.K., Hemminki, K. et al. Protein binding, sister chromatid exchange and expression of oncogene proteins in patients treated with cisplatinum (cisDDP)-based chemotherapy. Arch Toxicol 64, 401–406 (1990). https://doi.org/10.1007/BF01973463
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DOI: https://doi.org/10.1007/BF01973463