Role of hydroxymethyl sulfate esters in aromatic hydrocarbon carcinogenesis.

The unified hypothesis, for the carcinogenic properties of aromatic hydroca rbons, predicts that hydroxylation of meso-methyl groups followed by the fo rmation of electrophilic esters bearing a good leaving group, such as sulfa te, phosphate, or acetate, play a role in the DNA damage, mutagenesis and c arcinogenesis of alkyl-substituted hydrocarbons such as 7,12-dimethylbenz[a ] anthracene, 3-methyl-cholanthrene, and 6-methylbenzo[a]pyrene, and even u nsubstituted hydrocarbons such as benzo[a]pyrene. Activation of hydroxyalky l metabolites to electrophilic mutagens has been shown to be catalyzed by 3 '-phosphoadenosine-5'-phosphosulfate-dependent sulfotransferase activity. R ecent studies demonstrate that a number of sulfate esters account for most, if not all, of the complete carcinogenic activity of their hydroxyalkyl pr ecursors by repeated s.c. injection in female Sprague-Dawley rats. In addit ion to hydroxymethyl hydrocarbons, some aromatics with secondary benzylic h ydroxyl groups are also metabolically activated through sulfuric acid ester ification to electrophilic mutagens and potential ultimate carcinogens.