Effect of cadmium exposure on background and anti-5 methylchrysene-1,2-dihydrodiol 3,4-epoxide-induced mutagenesis in the supF gene of pS189 in human Ad293 cells

Chemical Research in Toxicology
R R MisraA Dipple

Abstract

Cadmium is a toxic environmental contaminant that is carcinogenic in humans and rodents. Although cadmium has proven to be mutagenic in a variety of assay systems, exactly how cadmium achieves gentoxicity is poorly understood. To define the mechanism(s) underlying the mutagenicity and comutagenicity of cadmium, human Ad293 cells were exposed to subtoxic doses of the metal and transfected with untreated or anti-5-methylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated pS189 shuttle vector. Alterations in the frequency, types, and distribution of mutations were subsequently assessed in the supF gene of pS189 that was replicated in Ad293 cells and screened in indicator bacteria. Doses of 0.5 and 1 microM CdCl2 increased the mutation frequency of untreated pS189 by approximately 4- and 8-fold, respectively, with no apparent effect on the types of mutations generated. In contrast, host-cell exposure to cadmium had little or no effect on the frequency, types, or distribution of mutations generated with 5-MCDE-treated pS189. These results indicate that cadmium increases mutagenesis of untreated pS189 by affecting a process that is not involved in mutagenesis of the 5-MCDE-treated vector. Although it is not clear exactly how host-c...Continue Reading

Citations

Jan 12, 2000·Journal of Biochemical and Molecular Toxicology·L E Rikans, T Yamano
Dec 4, 2003·Mutation Research·Michael P Waalkes
May 9, 2000·Toxicology and Applied Pharmacology·C YuanM P Waalkes
Sep 5, 2002·Environmental and Molecular Mutagenesis·M Vijayaraj ReddySheila M Galloway
Jun 30, 2005·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Pham T N DiepCatherine Jumarie

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