Bioactivation of Cyclopenta- and Cyclohexa-Fused Polycyclic Aromatic Hydrocarbons via the Formation of Benzylic Sulfuric Acid Esters

Abstract

There has been accumulated evidence that sulfo-conjugation plays an important role in the formation of electrophilic, mutagenic, and tumorigenic sulfuric acid ester metabolites from some hydroxymethyl aromatic hydrocarbons. In the present study, we have investigated whether sulfotransferases can also activate cyclopenta- and cyclohexa-fused polycyclic aromatic hydrocarbons containing secondary benzylic hydroxyl group(s). Thus, 3,4-dihydroxy-3,4-dihydrocyclopenta[cd]pyrene, as well as its monohydroxy analogs, covalently bound to DNA when incubated with rat liver cytosol and the sulfo-group donor, 3′-phosphoadenosine-5′-phosphosulfate. Likewise, 7-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene was activated to form an electrophilic and mutagenic species through sulfuric acid esterification. However, neither benzo[a]pyrene-7,8-dihydrodiol nor 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene produced reactive species in the presence of sulfotransferase activity.

Key Words:

• sulfotransferases
• metabolic activation
• benzylic sulfate esters
• cyclopenta-fused PAH
• mutagenicity
• sulfate conjugation.