Substance-dependent sex differences in the activation of benzylic alcohols to mutagens by hepatic sulfotransferases of the rat

Six primary and 10 secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of varying amounts of hepatic cytosol from adult male and female rats and 3'-phosphoadenosine-5'-phosphosulfate, the cofactor for sulfotransferases. With the exception of 1-(9-anthryl)ethanol, 4H-cyclopenta[def]-phenanthren-4-ol and 10-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, all the benzylic alcohols were activated to mutagens. For 1-(1-pyrenyl)ethanol (1-HEP), 1-(2-pyrenyl)ethanol (2-HEP), 6-hydroxymethylanthanthrene (6-HMAA), 2-hydroxymethylpyrene (2-HMP), 10H-indeno[1,2,7,7a-bcd]pyren-10-ol (OH-IP), 3-hydroxy-3,4-dihydrocyclopenta[cd]pyrene (3-OH-H2-CPcdP) and 1-(6-benzo[a]pyrenyl)ethanol (6-HEBP), this is the first observation of a mutagenic activity. The primary alcohols 1-hydroxymethylpyrene, 2-HMP, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 6-hydroxymethylbenzo[a]pyrene, as well as the secondary alcohols 1-HEP and 3-OH-H2-CPcdP, were more efficiently activated by hepatic cytosol from females than by preparations from males (2.6- to 8-fold). A further compound, 6-HEBP showed significant, but relatively weak, effects in the presence of cytosol from females, whereas it was inactive in the presence of hepatic cytosol from males. The reverse sex difference was observed in the activation of 4H-cyclo-penta[def]chrysen-4-ol, the activity of cytosol from males amounting to about four times that from females. Four other compounds, 2-HEP, 7-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, 6-HMAA and OH-IP, were activated with similar efficiency by hepatic cytosol from both sexes (< two-fold differences). The study indicates that different sulfotransferases are involved in the bioactivation of benzylic alcohols, including forms preferentially expressed in females as well as forms preferentially expressed in males, and that these enzymes qualitatively differ in their substrate tolerance for benzylic alcohols.