Rodent species and strain specificities for sister-chromatid exchange induction and gene mutagenesis effects from ethyl carbamate, ethyl N-hydroxycarbamate, and vinyl carbamate.
Ethyl carbamate (EC) and two related carcinogens, ethyl N-hydroxycarbamate (ENHC) and vinyl carbamate (VC), caused species-specific increases in sister-chromatid exchange (SCE) formation in the bone marrow cells of rodents. Mice exposed to 400 mg/kg of EC had SCE increases of 6-times-baseline, while rats, Chinese hamsters, and golden hamsters showed 3- to 4-times-baseline increases in response to this dose. Lesser, but still significant, differences were found for ENHC and VC; the severest effects consistently occurred in mice. Control bone marrow cell-cycle kinetics among the rodent species were similar. Mouse strains A and C57BL/6, which have high and low susceptibilities to EC induction of lung adenomas, respectively, showed nearly identical levels of SCE induction after in vivo exposure to these carbamates. However, testing of VC, a possible metabolite of EC, in vitro revealed strain-dependent liver enzyme (Aroclor-induced S-9 fraction) capabilities to convert VC to genotoxic products. SCE induction, gene mutation for 6-thioguanine and ouabain resistance, and cytotoxicity in Chinese hamster V79 cells were significantly greater when A strain S-9 enzymes were used as compared with C57BL/6 strain S-9 enzyme preparations. No effect on SCE of reseeding, compared with no reseeding, of VC-treated V79 cells was observed. At a concentration of 25 micrograms/ml, VC caused 6-times-baseline induction of SCE in the presence of A strain S-9 mix and 4-times-baseline induction in the presence of C57BL/6 strain S-9 mix. These in vitro strain-dependent patterns of response are relevant to the current theory that VC may be a proximate carcinogenic metabolite of EC.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000187:drug effects*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000187:drug effects*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014520:Urethane / Q000031:analogs & derivatives* / Q000494:pharmacology*
D002219:Carbamates; D006877:Hydroxamic Acids; D014520:Urethane; C011286:N-hydroxyurethane; C017963:vinyl carbamate