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Effects of Chronic Ethanol Consumption on Benzo(a)pyrene Metabolism and Glutathione S-Transferase Activities in Syrian Golden Hamster Cheek Pouch and Liver¹

Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595

The metabolism of benzo(a)pyrene (BaP) by hepatic or cheek pouch epithelium microsomes obtained from Syrian golden hamsters which had been consuming an ethanol-containing liquid diet for 4 wk and from pair-fed controls was measured. Glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene or (±)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)-pyrene as substrates was measured in cytosol obtained from the liver or cheek pouch epithelium of the same animals. Cytosolic hepatic glutathione levels were measured in both ethanol-consuming and control animals. The metabolism of BaP to 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene (BaP-4,5-diol), 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BaP-7,8-diol), 9-hydroxybenzo(a)pyrene (9-OH-BaP), and 3-hydroxybenzo(a)pyrene (3-OH-BaP) by hepatic microsomes from ethanol-consuming hamsters was significantly reduced (40–52%) (P < 0.05) compared to control microsomes. However, a 2-fold increase (P < 0.05) in the metabolism of BaP to BaP-7,8-diol and 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene was measured with microsomes from the cheek pouch epithelium of ethanol-consuming animals. There was no significant change in the production of BaP-4,5-diol, 9-OH-BaP, or 3-OH-BaP by cheek pouch epithelium microsomes of ethanol-consuming hamsters compared to controls. No difference in glutathione S-transferase activity of hepatic or cheek pouch epithelium cytosol between control and ethanol-consuming hamsters towards 1-chloro-2,4-dinitrobenzene or (±)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was observed. Hepatic glutathione content was significantly (P < 0.05) decreased after 2 wk (23%) and 4 wk (33%) of ethanol consumption. The results suggest a mechanism by which ethanol might enhance BaP tumorigenesis in the hamster cheek pouch.

¹ This study was supported by National Cancer Institute Grant CA-32617. This is paper No. 85 in "A Study of Chemical Carcinogenesis."

² To whom requests for reprints should be addressed.

Received 2/ 5/85. Revised 8/23/85. Accepted 10/ 4/85.

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