title: Bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver bile acid sulfotransferase I.
abstract: The bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene (HMBA) to an electrophilic sulfuric acid ester metabolite has been shown to be catalyzed by rat liver bile acid sulfotransferase I (BAST I). The sulfation and activation of HMBA by BAST I was determined by the ability of sulfated HMBA to form DNA adducts. The BAST I was also shown to react with rabbit anti-human dehydroepiandrosterone sulfotransferase antisera and to represent a major form of hydroxysteroid/bile acid sulfotransferase in female rat liver cytosol. Higher levels of BAST I activity and immunoreactivity as well as HMBA-DNA adduct formation were detected in female rat liver cytosol than in male rat liver cytosol. The bioactivation of HMBA by pure BAST I was dependent on the presence of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the reaction and was inhibited by dehydroepiandrosterone, a physiological substrate for BAST I. Glutathione, a cellular nucleophile with important protective properties, decreased DNA adduct formation in the HMBA sulfation reaction in the absence of glutathione S-transferase activity. These results indicate the usefulness of BAST I to investigate the sulfation and activation of HMBA and probably other hydroxymethylated polyaromatic hydrocarbons to electrophilic and mutagenic metabolites under defined reaction conditions.
authors.affiliation: Department of Pharmacology, University of Alabama, Birmingham 35294.
authors.forename: C N
authors.initials: CN
authors.lastname: Falany
authors.forename: J
authors.initials: J
authors.lastname: Wheeler
authors.forename: L
authors.initials: L
authors.lastname: Coward
authors.forename: D
authors.initials: D
authors.lastname: Keehan
authors.forename: J L
authors.initials: JL
authors.lastname: Falany
authors.forename: S
authors.initials: S
authors.lastname: Barnes
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D015238:Sulfotransferases; C019786:bile-salt sulfotransferase