Sister-chromatid exchange

Teratogenic effects have been noted with 2- and 4-aminophenol in the hamster, but 3-aminophenol was without effect in the hamster and rat (129,130). 4-Aminophenol is known to inhibit DNA synthesis and alter DNA stmcture in human lymphoblasts (131,132) and is mutagenic in mouse micronuclei tests (133). The aminophenols have been shown to be genotoxic, as evidenced by the induction of sister chromatid exchanges (134,135), but they also exert a protective effect against DNA interaction with other noxious chemicals (136). After assessment of available data a recent report stated that the aminophenols were safe as cosmetic ingredients in their present uses and concentrations (137). 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

Mitomycin C was found to have broad activity against a range of tumors and has been used clinically since the early 1960s [14, 15]. It causes many specific cellular effects, including inhibition of DNA synthesis, recombination, chromosome breakage, sister chromatid exchange, induction of DNA repair, and induction of... 

Sister chromatid exchange Sister chromatid exchange Sister chromatid exchange Sister chromatid exchange... 

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

Carrano AV, Thompson LH, Lindl PA, et al. 1978. Sister-chromatid exchange as an indicator of mutagenesis. Nature 271 551-553. 

Chen HH, Sirianni SR, Huang CC. 1982. Sister chromatid exchanges in Chinese hamster cells treated with seventeen organophosphorus compounds in the presence of a metabolic activation system. Environ Mutagen 4 621-624. 

Chen MM, Hsueh JE, Sirianni SR, et al. 1981. Induction of sister-chromatid exchanges and cell cycle delay in cultured mammalian cells treated with eight organophosphorus pesticides. Mutat Res 88 307-316. 

Das P, John G. 1999. Induction of sister chromatid exchanges and chromosome aberrations in vivo in Etroplus suratensis (Bloch) following exposure to organophosphorus pesticides. Toxicol Lett 104 111-116. 

De Ferrari M, Artuso M, Bonassi S, et al. 1991. Cytogenic biomonitoring of an Italian population exposed to pesticides Chromosome aberration and sister-chromatid exchange analysis in peripheral blood lymphocytes. Mutat Res 260 105-113. 

Dulout FN, Pastori MC, Olivero OA, et al. 1985. Sister-chromatid exchanges and chromosomal aberrations in a population exposed to pesticides. Mutat Res 143 237-244. 

Gomez-Arroyo S, Noriega-Aldana N, Juarez-Rodriguez D, et al. 1987. Sister chromatid exchanges induced by the organophosphorus insecticides methyl parathion, dimethoate, phoxim and methyl azinphos in cultured human lymphocytes. Contaminacion Ambiental 3 63-70. 

Sirianni SR, Huang CC. 1980. Comparison of induction of sister chromatid exchange, 8-azaguanine- and ouabain-resistant mutants by cyclophosphamide, ifosfamide and l-(pyridyl-3)-3,3-dimethyltriazene in Chinese hamster cells cultured in diffusion chambers in mice. Carcinogenesis 1 353-355. 

Cultured human lymphocytes Sister chromatid exchange + + Sobti et al. 1983... 

Figure 36-12. Sister chromatid exchanges between human chromosomes. These are detectabie by Giemsa staining of the chromosomes of ceiis repiicated for two cycies in the presence of bromodeoxyuridine. The arrows indicate some regions of exchange. (Courtesy of S Wolff and J Bodycote.)...

Chromosomal aberrations Gene mutation Dominant lethal mutation Micronucleus formation Micronucleus formation Micronucleus formation Chromosomal aberrations Sister chromatid exchange Micronucleus formation Chromosomal aberrations Sister chromatid exchange DNA-protein cross-links Nondisjunction of Y chromosome in sperm DNA damage (single-strand breaks)... 

Human (occupational exposure) Sister chromatid exchange (+) Gu et al. 1981... 

Gu ZW, Sele B, Jalbert P, et al. 1981. Induction of sister chromatid exchange by trichloroethylene and its metabolites. Toxicol Eur Res 3 63-67. (French)... 

Nagaya T, Ishikawa N, Hata H. 1989a. Sister-chromatid exchanges in lymphocytes of workers exposed to trichloroethylene. Mutat Res 222 279-282. 

Seiji K, Jin C, Watanabe T, et al. 1990. Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with references to smoking habits. Int Arch Occup Environ Health 62 171-176. 

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