REACTION OF ADENINE WITH 6-HYDROXYESTROGEN 6-SULFATES - MODEL COMPOUNDS TO DEMONSTRATE CARCINOGENESIS BY ESTROGEN

To examine carcinogenesis by estrogens, we investigated the reactivity of 6-hydroxyestrogen 6-sulfates. Two epimeric 6-sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl sulfate(1) and its 6 beta-is omer (2), were synthesized as model compounds and reacted with adenine under mild conditions to give two common products in the ratios of ap proximately 3:1 and 5:1, respectively, The major product was identifie d as N-6-[3-methoxyestra-1,3,5(10)-trien-6 beta-yl] adenine (10), acco mpanied with its 6 alpha-isomer (9), by comparison with synthetic spec imens, These results imply that, in the metabolism of naturally occurr ing estrogens, hydroxylation at the C-6-position and subsequent sulfoc onjugation of the benzylic hydroxyl group may produce sulfates which r eact with DNA to initiate carcinogenesis.