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 developing lungs, juvenile ferrets were exposed to ETS at an average total particulate concentration of 381 +/- 97 mg/m3 for 2 h at the breathing zone. Twenty-four hours after the exposure, the ferrets were sacrificed 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 carcinogen (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10- epoxide was twofold higher in the liver than that observed in the lung of control ferrets. After 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 protein-bound metabolites were significantly increased in the liver after ETS exposure. Although glutathione conjugates tended to be increased both in the lung and liver, sulfate conjugates were significantly decreased in the lung after ETS exposure (p < .05). (+)-trans-Benzo[a]pyrene-7,8-dihydrodiol was used to study the relative contributions of cytochrome P-450 and peroxyl radical-mediated formation of benzo[a]-pyrene-7,8-dihydrodiol-9,10-epoxide. Peroxyl radical- and P-450-mediated conversion of (+)-trans-benzo[a]pyrene-7,8-dihydrodiol to benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide was proportionately equal in the ferret lung, whereas in the liver the P-450-mediated pathway was predominant. After ETS exposure there was a tendency for P-450-mediated formation of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to increase. These results demonstrate significant differences in the metabolism of (-)-trans-benzo[a]pyrene-7,8-dihydrodiol by the lung and liver of juvenile ferrets and suggest a significant role of peroxyl radical-mediated formation of (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide in the lung, which may help explain discrepancy between the levels of P-450 and amounts of DNA adducts of polycyclic aromatic hydrocarbons in different organs in smokers.
Sindhu
R K
RK
Department of Pathology, College of Medicine, University of California at Irvine 92717, USA.
Rasmussen
R E
RE
Kikkawa
Y
Y
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000818:Animals; D005289:Ferrets; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide