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.