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-dihydroxymethylbenz[a]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-hydroxymethylbenz[a]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.
Watabe
T
T
Hiratsuka
A
A
Ogura
K
K
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013466:Sulfurtransferases / Q000378:metabolism
D001551:Benz(a)Anthracenes; C046810:7,12-dihydroxymethylbenz(a)anthracene; D005982:Glutathione Transferase; D013466:Sulfurtransferases; D005978:Glutathione