Regioselective glutathione conjugation of the carcinogen, 7, 12-dihydroxymethylbenz[a]anthracene, via reactive 7-hydroxymethyl sulfate ester in rat liver cytosol

Potent mutagenicity of 7,12-dihydroxymethylbenza]anthracene (DHBA) toward Salmonella typhimurium TA 98 in the presence of rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate (PAPS) was completely retarded by the addition of glutathione (GSH). The reactive and intrinsically mutagenic metabolite, DHBA 7-sulfate, formed by hepatic cytosolic sulfotransferase disappeared from the incubation mixture by the addition of GSH. Non-mutagenic S-(12-hydroxymethylbenza]anthracen-7-yl)methylglutathione was isolated from the incubation mixture consisting of the hepatic cytosol, DHBA, PAPS, and GSH and proved to be formed by GSH S-transferase directly from DHBA 7-sulfate as an obligatory intermediate.