EFFECT OF ENVIRONMENTAL TOBACCO-SMOKE ON THE METABOLISM OF (-)-TRANS-BENZO[A]PYRENE-7,8-DIHYDRODIOL IN JUVENILE FERRET LUNG AND LIVER

To evaluate the effects of ''environmental tobacco smoke'' (ETS) on de veloping lungs, juvenile ferrets were exposed to ETS at an average tot al particulate concentration of 381 +/- 97 mg/m(3) for 2 h at the brea thing zone. Twenty-four hours after the exposure, the ferrets were sac rificed and the metabolism of (-)-trans-benzo[a]pyrene-7,8-dihydrodiol was studied in the lung and liver homogenates. The rate of conversion of (-)-trans-benzo[a]pyrene-7,8-dihydrodiol to the ultimate carcinoge n )-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide was twofold highe r in the liver than that observed in the lung of control ferrets. Afte r ETS exposure, the formation of free benzo[a]pyrene-7,8-dihydrodiol-9 ,10-epoxide was increased by 62% in the lung (p < .01). The DNA-bound metabolites were significantly increased only in the lung, while prote in-bound metabolites were significantly increased in the liver after E TS exposure. Although glutathione conjugates tended to be increased bo th in the lung and liver, sulfate conjugates were significantly decrea sed in the lung after ETS exposure (p < .05). (+)-trans-Benzo[a]pyrene -7,8-dihydrodiol was used to study the relative contributions of cytoc hrome P-450 and peroxyl radical-mediated formation of benzo[a]pyrene-7 ,8-dihydrodiol-9, 10-epoxide. Peroxyl radical- and P-450-mediated conv ersion of (+)-trans-benzo[a]pyrene-7,8-dihydrodiol to benzo[a]pyrene-7 ,8-dihydrodiol-9, 10-epoxide was proportionately equal in the ferret l ung, whereas in the liver the P-450-mediated pathway was predominant. After ETS exposure there was a tendency for P-450-mediated formation o f benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to increase. These resul ts demonstrate significant differences in the metabolism of (-)-trans- benzo[a]pyrene-7,8-dihydrodiol by the lung and liver of juvenile ferre ts and suggest a significant role of peroxyl radical-mediated formatio n of (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-10-epoxide in the lung, w hich may help explain discrepancy between the levels of P-450 and amou nts of DNA adducts of polycyclic aromatic hydrocarbons in different or gans in smokers.