| Metal Mutagenesis in Transgenic Chinese Hamster Cell Lines Environ Health Perspect Key words: nickel sulfides, nickel oxides, chromium, mercury, gpt, mutagenesis
This paper was presented at the Second International Meeting on Molecular Mechanisms of Metal Toxiciity and Carcinogeniciity held 10-17 January 1993 in Madonna di Campiglio, Italy.
These studies were supported by NIH grant numbers ES 04895, ES 05512, and ES 04715 from the National Institute of Environmental Health Sciences and grant number R814702 from the US Environmental Protection Agency to M.C.; by NIH grant number CA 51825 from the National Cancer Institute to E.T.S.; and by NIEHS Center grant number 00260.
Address correspondence to Dr. Catherine B. Klein, Nelson Institute of Environmental Medicine, New York University Medical Center, 550 First Avenue, New York, NY 10016. Telephone (914) 531-5419. Fax (914) 351-2118.
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Metals are toxic agents for which genotoxic effects are often difficult to demonstrate. To study metal mutagenesis, we have used two stable hprt 2/ gpt1 transgenic cell lines that were derived from Chinese hamster V79 cells. Both the G12 and G10 cell lines are known to be very sensitive to clastogens such as X-rays and bleomycin, with the mutagenic response of the integrated xanthine guanine phosphoribosyl transferase (gpt) gene in G10 usually exceeding that of the same gene in the transgenic G12 cells. In studies with carcinogenic insoluble nickel compounds, a high level of mutagenesis was found at the gpt locus of G12 cells but not at the endogenous hypoxanthine phosphoribosyl transferase (hprt) locus of V79 cells. We have since demonstrated the similar recovery of a high frequency of viable G12 mutants with other insoluble nickel salts including nickel oxides (black and green) . The relative mutant yield for the insoluble nickel compounds (G12>G10) is the opposite of that obtained with nonmetal clastogens (G10>G12) . In the G12 cells, nickel mutagenesis may be related to the integration of the gpt sequence into a heterochromatic region of the genome. For some of the insoluble nickel compounds, significant inhibition of both cytotoxicity and mutant yield resulted when the G12 cells were pretreated with vitamin E. In comparison with the nickel studies, the mutagenic responses to chromium compounds in these cell lines were not as dramatic. Mutagenesis of the gpt target could not be demonstrated with other metals such as mercury or vanadium. -- Environ Health Perspect 102(Suppl 3) :63-67 (1994) . Key words: nickel sulfides, nickel oxides, chromium, mercury, gpt, mutagenesis
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