Bioalkylation of benz[a]anthracene, 7-methylbenz[a]anthracene, and 12-methylbenz[a]anthracene in rat lung cytosol preparations.
Benz[a]anthracene (BA) and the monomethyl meso-anthracenic or L-region derivatives 7-methylbenz[a]anthracene (7-methylBA) and 12-methylbenz[a]anthracene (12-methylBA) underwent a bioalkylation substitution reaction in rat lung ctyosol preparations, fortified with S-adenosyl-L-methionine to form the more potent carcinogen 7,12-dimethylbenz[a]anthracene. The methyl groups of the highly reactive L-region methylated metabolites also underwent enzymatic hydroxylation in rat lung cytosol preparations to yield the corresponding hydroxymethyl derivatives, 7-hydroxymethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, and 7,12-dihydroxymethylbenz[a]anthracene. The biooxidation reaction took place enzymatically, and exclusively, or nearly so, at the reactive methyl groups attached to the meso positions or L-region of the hydrocarbon. Bioalkylation and biooxidation reactions did not occur when the hydrocarbons were incubated with a boiled cytosol preparation, indicating the need for enzymatic activation of the L-region methyl groups. Also, the bioalkylation reaction did not occur in the absence of S-adenosyl-L-methionine. Furthermore, the S-adenosyl-L-methionine-dependent reaction was inhibited by S-adenosyl-L-homocysteine, suggesting that the reaction is catalyzed by a cytosolic S-adenosyl-L-methionine-dependent methyltransferase.