title: Mutagenicity of benzyl S-haloalkyl and S-haloalkenyl sulfides in the Ames-test.
abstract: The mutagenicity of benzyl 1,2,3,4,4-pentachlorobutadienyl sulfide (BPBS) and benzyl 1,2-dichlorovinyl sulfide (BDVS) was studied in the Ames preincubation assay to investigate the hypothesis that the mutagenic effect of the cysteine S-conjugates S-(pentachlorobutadienyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-cysteine is associated with their metabolism to unstable thiols. Under conditions enabling cytochrome P-450-dependent benzylic hydroxylation of BPBS and BDVS, both benzyl sulfides were mutagenic. These results in combination with the lack of mutagenicity observed with benzaldehyde and with the tert-butyl analogues, which cannot be metabolized to a hemimercaptal, indicate that the formation of unstable thiols is responsible for the mutagenic effects of the benzyl sulfides and the corresponding cysteine S-conjugates. Benzyl 2-chloro-1,1,2-trifluoroethyl sulfide, which also undergoes benzylic hydroxylation, was negative in the Ames-Test; this is in agreement with the observed lack of mutagenicity of the corresponding S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine. Also, benzyl 2-chloroethyl sulfide, which, along with the corresponding S-conjugate S-(2-chloroethyl)-L-cysteine, does not require bioactivation, was a potent, direct-acting mutagen in the Ames-Test.
authors.affiliation: Institut für Toxikologie, Universität Würzburg, Federal Republic of Germany.
authors.forename: S
authors.initials: S
authors.lastname: Vamvakas
authors.forename: W
authors.initials: W
authors.lastname: Dekant
authors.forename: M W
authors.initials: MW
authors.lastname: Anders
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D003545:Cysteine / Q000031:analogs & derivatives; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism / Q000633:toxicity*; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D001593:Benzyl Compounds; D013438:Sulfhydryl Compounds; D013440:Sulfides; D014020:Tissue Extracts; D003577:Cytochrome P-450 Enzyme System; D003545:Cysteine