Mutagenicity of Benzyl S-Haloalkyl and S-Haloalkenyl Sulfides in the Ames-Test. (Reannouncement with New Availability Information).

摘要

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-(pentachlorobutad ienyl)-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 ofunstable 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-chloroethylsulfide, 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.