Haloalcohols deplete glutathione when incubated with fortified liver fractions

1. This study has examined the ability of dichloropropanols, haloalcohols a nd their putative metabolites to deplete glutathione when incubated with li ver fractions obtained from untreated and differentially induced rats. 2. 1,3-Dichloropropan-2-ol and 2,3-dichloropropan-1-ol (0-1000 mu M) both d epleted glutathione in a dose-dependent manner when incubated with cofactor s (NADPH generating system) and liver microsomes from the untreated rat. 3. The extent of GSH depletion was significantly enhanced when liver micros omes from the isoniazid- or isosafrole-treated rat were used. 4. Epichlorohydrin produced a moderate, dose-dependent depletion of GSH. By contrast, 1,3-dichloroacetone (identified by TLC as a metabolite of 1,3-di chloropropanol) was a potent depletor of glutathione. 5. N-acetylcysteine was less efficient than glutathione as a nucleophile tr ap for epichlorohydrin, 1,3-dichloroacetone or reactive metabolites derived from 1,3-dichloropropan-2-ol. 6. 1,3-Dibromopropan-2-o1 and 1,4-dibromobutan-2-ol were potent depletors o f GSH but 1-bromopropan-2-ol produced less GSH depletion. Both dibromoalcoh ols depleted GSH when incubated with dialysed cytosol derived from the live rs of untreated rats. 7. The GSH depletion mediated by 1,3-dichloropropan-2-ol, 1,3-dibromopropan -2-ol, 1,4-dibromobutan-2-ol and 1-bromopropan-2-ol was inhibited by inclus ion of pyridine (1 mM) or cofactor omission. 1,3-Difluoropropanol did not d eplete GSH under any of the conditions examined.