Cisplatin-induced Cytogenetic Alterations In V79 Cells

Cisplatin is an antineoplastic agent used to treat solid malignancies, such as ovarian, testicular and bladder tumors. Studies have been shown that cisplatin induces genotoxic effects and chromosomal alterations that can result in genetic and chromosomal instability. In this work, we investigated the effects of cisplatin on the cytogenetic traits of cultured V79 cells based on the modal chromosome number, mitotic index, frequency of polyploidy and number of aneuploid metaphases. Cisplatin-treated V79 cells showed an altered chromosome number distribution, as well as an enhanced mitotic index, frequency of polyploidy and number of aneuploid metaphases. These alterations were probably related to the genetic instability produced by cisplatin. In addition, these cells showed characteristics associated with neoplastic development that corresponded to neoplastic processes related to the use of cisplatin in chemotherapy. © 2007 The Japan Mendel Society.722155160Allavena, P., Pirovano, P., Bonazzi, C., Colombo, N., Mantovani, A., D'Incalci, M., In vitro and in vivo effects of cisplatin on the generation of lymphokine-activated killer cells (1990) J. Natl. Cancer Inst, 82, pp. 139-142Barrett, J.C., Cell culture models of multistep carcinogenesis (1985) IARC Sci. Publ, 58, pp. 181-202Borenfreund, E., Babich, H., Martin-Alguacil, N., Effect of methylazoxymethanol acetate on bluegill sunfish cell cultures in vitro (1989) Ecotoxicol. Environ. Saf, 17, pp. 297-307Bradley, M.O., Bhuyan, B., Francis, M.C., Langenbach, R., Peterson, A., Huberman, E., Mutagenesis by chemical agents in V79 chinese hamster cells: A review and analysis of the literature. A report of the Gene-Tox Program (1981) Mutat. Res, 87, pp. 81-142Chambers, S.K., Chopyk, R.L., Chambers, J.T., Schwartz, P.E., Duffy, T.P., Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer (1989) Cancer, 64, pp. 2459-2461Chang, W., Little, J., Persistently elevated frequency of spontaneous mutations in progeny of CHO clones surviving X-irradiation: Association with delayed reproductive death phenotype (1992) Mutat. Res, 270, pp. 191-199Deitch, A.D., Sawicki, S.G., Effects of cordycepin on microtubules of cultured mammalian cells (1979) Exp. Cell Res, 118, pp. 1-13Genari, S.C., Wada, M.L.F., Behavioural differences and cytogenetical analysis of a transformed cellular population derived from a Vero cell line (1995) Cytobios, 81, pp. 17-25Genari, S.C., Wada, M.L.F., Dolder, M.A.H., Wada, M.L.F., Scanning and transmission electron microscopy of transformed Vero cells, with altered in vitro growth characteristics (1996) J. Submicrosc. Cytol. Pathol, 28, pp. 565-572Genari, S.C., Wada, M.L.F., Dolder, M.A.H., Wada, M.L.F., Wada, M.L.F., Effects of nutritional stress conditions on the ploidy and growth of human amniotic cells (2000) In Vitro Cell. Develop. Biol, 36, pp. 147-150Genari, S.C., Wada, M.L.F., Dolder, M.A.H., Wada, M.L.F., Wada, M.L.F., The influence of nutritional stress on the differentiation of epithelial cells in vitro (2003) Braz. J. Morphol. Sci, 20, pp. 135-140Giaccone, G., Clinical perspectives on platinum resistance (2000) Drugs, 59, pp. 9-17Gilvarry, U., Farrel, D., Lynch, V., Moriarty, M., Dooley, M., Law, E., Clynes, M., Cytological differences between normal and malignant human cell populations in culture (1990) Cancer Res, 50, pp. 3390-3393González, V.M., Fuertes, M.A., Alonso, C., Pérez, J.M., Is cisplatin-induced cell death always produced by apoptosis? (2001) Mol. Pharmacol, 59, pp. 657-663Hadnagy, W., Seemayer, N.H., Cytotoxic and genotoxic effects of extract of particulate emission from a gasoline-powered engine (1988) Environ. Mol. Mutagen, 12, pp. 385-396Harper, K., Lorimore, S., Wright, E., Delayed appearance of radiation-induced mutations at the Hprt locus in murine hematopoietic cells (1997) Exp. Hematol, 25, pp. 263-269Holliday, R., Chromosome error propagation and cancer (1989) Trends Genet, 5, pp. 42-45Little, J., Induction of genetic instability by ionizing radiation (1999) C. R. Acad. Sci. III, 322, pp. 127-134Lothschutz, D., Jennewein, M., Pahl, S., Lausberg, H.F., Eichler, A., Mutschler, W., Hanselmann, R.G., Oberringer, M., Polyploidization and centrosome hyperamplification in inflammatory bronchi (2002) Inflamm. Res, 51, pp. 416-422Mead, G.M., Green, J.A., Macbeth, F.R., Williams, C.J., Whitehouse, J.M., Buchanan, R., Second malignancy after cisplatin, vinblastine, and bleomycin (PVB) chemotherapy: A case report (1983) Cancer Treat. Rep, 67, p. 410Ohshima, S., Induction of genetic instability and chromosomal instability by nickel sulfate in V79 Chinese hamster cells (2003) Mutagenesis, 18, pp. 133-137Reedjik, J., The mechanism of action of platinum anti-cancer drugs (1987) Pure Appl. Chem, 59, pp. 181-192Rosenberg, B., VanCamp, L., Trosko, J.E., Mansour, V.H., Platinum compounds: A new class of potent antitumor agents (1969) Nature, 222, pp. 385-386Srb, V., Prochazkova, J., Monitoring of effects of cis-diamminedichloroplatinum II. Part I. Cytogenetic analysis in vitro (1983) Neoplasma, 30, pp. 463-467Storchova, Z., Pellman, D., From polyploidy to aneuploidy, genome instability and cancer (2004) Nat. Rev. Mol. Cell. Biol, 5, pp. 45-54Tandon, P., Sodhi, A., cis-Dichlorodiammine platinum (II) induced aberrations in mouse bone-marrow chromosomes (1985) Mutat. Res, 156, pp. 193-197Turnbull, D., Popescu, N.C., DiPaolo, J.A., Myhr, B.C., cis-platinum(II)diammine dichloride causes mutation, transformation, and sister-chromatid exchanges in cultured mammalian cells (1979) Mutat. Res, 66, pp. 267-275Van Imhoff, G.W., Sleijfer, D.T., Breuning, M.H., Anders, G.J., Mulder, N.H., Halie, M.R., Acute nonlymphocytic leukemia 5 years after treatment with cisplatin, vinblastine, and bleomycin for disseminated testicular cancer (1986) Cancer, 57, pp. 984-987Wiencke, J.K., Cervenka, J., Paulus, H., Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II (1979) Mutat. Res, 68, pp. 69-77Zhu, H., Gooderham, N., Neoplastic transformation of human lung fibroblast MRC-5 SV2 cells induced by benzo[a]pyrene and confluence culture (2002) Cancer Res, 62, pp. 4605-460