Mutagenicity of the cysteine S-conjugate sulfoxides of trichloroethylene and tetrachloroethylene in the Ames test.

Roy M Irving, Adnan A Elfarra

Toxicology 2013 Apr 05

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The nephrotoxicity and nephrocarcinogenicity of trichloroethylene (TCE) and tetrachloroethylene (PCE) are believed to be mediated primarily through the cysteine S-conjugate β-lyase-dependent bioactivation of the corresponding cysteine S-conjugate metabolites S-(1,2-dichlorovinyl)-l-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-l-cysteine (TCVC), respectively. DCVC and TCVC have previously been demonstrated to be mutagenic by the Ames Salmonella mutagenicity assay, and reduction in mutagenicity was observed upon treatment with the β-lyase inhibitor aminooxyacetic acid (AOAA). Because DCVC and TCVC can also be bioactivated through sulfoxidation to yield the potent nephrotoxicants S-(1,2-dichlorovinyl)-l-cysteine sulfoxide (DCVCS) and S-(1,2,2-trichlorovinyl)-l-cysteine sulfoxide (TCVCS), respectively, the mutagenic potential of these two sulfoxides was investigated using the Ames Salmonella typhimurium TA100 mutagenicity assay. The results show both DCVCS and TCVCS were mutagenic, and TCVCS exhibited 3-fold higher mutagenicity than DCVCS. However, DCVCS and TCVCS mutagenic activity was approximately 700-fold and 30-fold lower than DCVC and TCVC, respectively. DCVC and DCVCS appeared to induce toxicity in TA100, as evidenced by increased microcolony formation and decreased mutant frequency above threshold concentrations. TCVC and TCVCS were not toxic in TA100. The toxic effects of DCVC limited the sensitivity of TA100 to DCVC mutagenic effects and rendered it difficult to investigate the effects of AOAA on DCVC mutagenic activity. Collectively, these results suggest that DCVCS and TCVCS exerted a definite but weak mutagenicity in the TA100 strain. Therefore, despite their potent nephrotoxicity, DCVCS and TCVCS are not likely to play a major role in DCVC or TCVC mutagenicity in this strain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Citation

Roy M Irving, Adnan A Elfarra. Mutagenicity of the cysteine S-conjugate sulfoxides of trichloroethylene and tetrachloroethylene in the Ames test. Toxicology. 2013 Apr 05;306:157-61