A 7-hydroxymethyl sulphate ester as an active metabolite of the carcinogen, 7-hydroxymethylbenz[a]anthracene.
7-Hydroxymethylbenz[a]anthracene (7-HBA) showed potent mutagenicity towards Salmonella typhimurium TA 98 in the presence of untreated rat liver cytosol fortified with the PAPS-generating system, sodium sulphate and ATP. No mutagenic activity was observed either when the cytosol was boiled or when sodium sulphate or ATP was omitted from the assay medium. A highly reactive sulphate ester of 7-HBA was isolated and identified from the medium. It had a half-life of 3.5 min at 37 degrees C and pH 7.4 in water and showed potent, intrinsic mutagenicity towards TA 98. The mutagenicity of 7-HBA sulphate was almost completely retarded in the presence of the cytosol and glutathione. From the biological systems containing glutathione a non-mutagenic and stable glutathione conjugate was isolated that was assigned as S-(benz[a]anthracen-7-yl)methylglutathione. 7-HBA sulphate covalently bound to calf thymus DNA and cytosolic proteins. A fluorospectroscopic study indicated that the carcinogen bound to the biomacromolecules through its 7-methylene group with loss of a sulphate anion as a leaving group.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002911:Chrysenes / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004952:Esters; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism*
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D002911:Chrysenes; D004952:Esters; D013431:Sulfates; C025909:7-hydroxymethylbenz(a)anthracene; D006881:Hydroxyacetylaminofluorene; C032670:5-hydroxymethylchrysene; D004247:DNA; D005982:Glutathione Transferase; D005978:Glutathione