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

Cadmium is a toxic environmental contaminant that is carcinogenic in h umans and rodents. Although cadmium has proven to be mutagenic in a va riety of assay systems, exactly how cadmium achieves gentoxicity is po orly understood. To define the mechanism(s) underlying the mutagenicit y and comutagenicity of cadmium, human Ad293 cells were exposed to sub toxic doses of the metal and transfected with untreated or anti-5-meth ylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated pS189 shuttle vector. Alterations in the frequency, types, and distribution of mutat ions were subsequently assessed in the supF gene of pS189 that was rep licated in Ad293 cells and screened in indicator bacteria. Doses of 0. 5 and 1 mu M 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 distrib ution of mutations generated with 5-MCDE-treated pS189. These results indicate that cadmium increases mutagenesis of untreated pS189 by affe cting a process that is not involved in mutagenesis of the 5-MCDE-trea ted vector. Although it is not clear exactly how host-cell exposure to cadmium increases background mutagenesis, presumably, the mutagenic e ffect does not involve cadmium interaction with the cellular machinery used to replicate past bulky DNA lesions.