LACK OF RESPONSE OF THE RAT-LIVER CLASS-3 CYTOSOLIC ALDEHYDE DEHYDROGENASE TO TOXIC-CHEMICALS, GLUTATHIONE DEPLETION, AND OTHER FORMS OF STRESS

One of the rat liver ''Class 3'' cytosolic aldehyde dehydrogenases (EC 1.2.1.3), ALDH3c, is known to be markedly induced by polycyclic aroma tic hydrocarbons and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin ). In the present study we examined whether hepatic ALDH3c induction i s a general response to toxicity. Treatment of Wistar rats for 4 days with known toxic doses of hepatotoxic agents-carbon tetrachloride, dim ethylnitrosamine, diethylnitrosamine, aflatoxin B-1 and D-ethionine-di d not induce ALDH3c enzyme activity. Whereas dimethylaminoazobenzene a t 100 mg/kg/day for 4 days did not increase ALDH3c, a 10-fold lower do se of dimethylaminoazobenzene for 4 days produced a 20-fold increase i n ALDH3c activity. Treatment with phorone, diethylmaleate or L-buthion ine-S,R-sulfoximine-which deplete reduced glutathione (GSH) by differe nt mechanisms-did not affect ALDH3c activity. One dose of benzo[a]pyre ne for 24 hr increased ALDH3c activity by 25-fold. Treatment with both the GSH-depleting chemicals and benzo[a]pyrene inhibited ALDH3c induc tion by 45% to 75%, suggesting a role for GSH during ALDH3c induction. After ALDH3c activity had already been induced by benzo[a]pyrene, how ever, the GSH-depleting chemicals did not affect ALDH3c activity. No c hanges in ALDH3c activity were seen 24 or 48 hr after partial hepatect omy, on the fifth day following surgical cholestasis, or after guaneth idine-induced sympathectomy. These data indicate that hepatic ALDH3c i nducibility in the rat is not a general or direct response to chemical toxicity, or to conditions of GSH depletion or other forms of stress.