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-isomer (2), were synthesized as model compounds and reacted with adenine under mild conditions to give two common products in the ratios of approximately 3:1 and 5:1, respectively. The major product was identified as N6-[3-methoxyestra-1,3,5(10)-trien-6 beta-yl] adenine (10), accompanied with its 6 alpha-isomer (9), by comparison with synthetic specimens. These results imply that, in the metabolism of naturally occurring estrogens, hydroxylation at the C6-position and subsequent sulfoconjugation of the benzylic hydroxyl group may produce sulfates which react with DNA to initiate carcinogenesis.
Itoh
S
S
Hokkaido College of Pharmacy, Japan.
Yamauchi
A
A
Itoh
Y
Y
Takagi
H
H
Yoshizawa
I
I
D000225:Adenine / Q000737:chemistry*; D001711:Biotransformation; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity; D004963:Estrenes / Q000737:chemistry* / Q000633:toxicity; D004967:Estrogens / Q000737:chemistry / Q000633:toxicity; D007536:Isomerism; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000633:toxicity
D002273:Carcinogens; D004963:Estrenes; D004967:Estrogens; D011726:Pyridinium Compounds; C070233:pyridinium 3-methoxyestra-1,3,5(10)-trien-6-yl sulfate; D000225:Adenine