BIOACTIVATION OF BENZYLIC AND ALLYLIC ALCOHOLS VIA SULFO-CONJUGATION

Although sulfo-conjugation, in general, has been regarded as a detoxif ication process in the xenobiotic metabolism, there is a substantial b ody of data supporting that the same reaction can also lead to activat ion of certain types of chemical carcinogens and mutagens. Examples in clude some aromatic amines and amides, alkenylbenzenes, methyl-substit uted polyaromatic hydrocarbons, nitrotoluenes and nitrosamines. The N- or O-hydroxy derivatives of these compounds undergo sulfonation to fo rm extremely reactive sulfuric acid esters that can play a role as ult imate carcinogenic/mutagenic metabolites. Previous studies from severa l laboratories have shown that hydroxymethyl polyarenes, such as hydro xymethylbenz[a]anthracenes, 6-hydroxymethylbenzo[a]pyrene, and 1-hydro xymethylpyrene, are activated to reactive benzylic sulfuric acid ester s, preferentially by rat hepatic hydroxysteroid sulfotransferase. Some aromatic hydrocarbons bearing the secondary benzylic hydroxy function ality can also yield electrophilic sulfate esters in the presence of h epatic sulfotransferase activity. Thus, benzylic mono- and dihydroxy d erivatives of cyclopenta[cd]pyrene form mutagenic and DNA binding spec ies when incubated with rat liver cytosol and the sulfo-group donor, 3 '-phosphoadenosine-5'-phosphosulfate. 1-Hydroxy-3-methylcholanthrene t hat also possesses the cyclopenta-fused ring system appears to be meta bolically activated through sulfo-conjugation. Likewise, benzo[a]pyren e tetraol might be activated through sulfuric acid esterification at o ne cf two benzylic hydroxyl groups. Methylene-bridged polyarenols repr esent another potential group of cyclic secondary benzylic alcohols th at can be activated by sulfotransferases. Certain non-polycyclic aroma tic type benzylic alcohols have also been proposed to undergo sulfotra nsferase-mediated activation. Besides benzylic sulfonation, sulfuric a cid esterification of certain allylic alcohols can produce reactive sp ecies. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.