Lung metabolism of benzo[a]pyrene in rats treated with p‐xylene and/or ethanol

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Abstract
The metabolism of benzo[a]pyrene (BaP) may be altered by xenobiotic compounds. The effects of p‐xylene and ethanol on the lung metabolism of BaP were studied. p‐Xylene was administered by ip injection at doses ranging from 0.1 to 1.0 g/kg (1:1 in soybean oil). Ethanol was administered po at 5 g/kg (40% w/v). Rats given p‐xylene, ethanol, or p‐xylene and ethanol were sacrificed 1 h after treatment. Additional time points of 75 min, 30 min, 4 h, and 24 h after p‐xylene (1 g/kg) were examined. 3‐Hy‐droxy‐BaP (3‐OH) formation was measured fluorometrically as aryl hydrocarbon hy‐droxylase activity (AHH) in lung microsomes. p‐Xylene (1 g/kg) inhibited the formation of 3‐OH BaP 40% at 15 min, 27% at 30 min, 43% at 1 h, and 39% at 4 h after treatment. Inhibition of AHH activity was still present 24 h after dosing (41%). AHH activity was inhibited 27% and 46% at 0.5 mg/kg and 1.0 mg/kg p‐xylene (1 h), respectively, while the lowest dose (0.7 mg/kg) did not change activity. Analysis of the major metabolites of BaP by high‐performance liquid chromatography (HPLC) demonstrated that the formation of 3‐OH and 4,5‐diol BaP were inhibited 32% and 50%, respectively, in lung microsomes prepared 24 h after a single injection of p‐xylene (1 glkg). None of the other metabolites analyzed were changed by p‐xylene. Ethanol had no effect on 3‐OH BaP formation during a 1‐h treatment. A combined dose of ethanol and p‐xylene moderately inhibited 3‐OH BaP formation. These findings indicate that BaP detoxication (i.e., 3‐OH formation) in rat lung is selectively inhibited by p‐xylene but not ethanol. Ethanol appears to modify the inhibitory effect of p‐xylene.