Rk. Sindhu et al., EFFECT OF ENVIRONMENTAL TOBACCO-SMOKE ON THE METABOLISM OF (-)-TRANS-BENZO[A]PYRENE-7,8-DIHYDRODIOL IN JUVENILE FERRET LUNG AND LIVER, Journal of toxicology and environmental health, 45(4), 1995, pp. 453-464
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.