Benzo(a)pyrene oxidation, conjugation and disposition in the isolated perfused rabbit lung: role of the glutathione S-transferases.
The isolated perfused rabbit lung metabolised 7--11 % of 20 mumol of [14C]-benzo(a)pyrene added in the perfusion medium in 1 h. The major metabolite formed was 3-hydroxybenzo(a)pyrene, both free (30--40 % of the total metabolites) and conjugated (4 % of total metabolites). Quinones comprised 15 % of the total and metabolism at the 9, 10 position accounted for a further 10 %. Forty per cent of the water-soluble metabolites was chromatographically identical to the glutathione conjugate of benzo(a)pyrene 4,5-oxide. Sulphate and glucuronide conjugates were formed in small but detectable amounts, principally from phenols, but also from dihydrodiols. After 1 h the more water-soluble conjugates had diffused from the lung into the perfusion medium, but the majority (60--90 %) of the metabolic products were still concentrated within the lung. The lung's limited ability to conjugate its major metabolites of benzo(a)pyrene with sulphuric or glucuronic acid, coupled with slow elimination of the products formed, particularly dihydrodiols may contribute to the susceptibility of this organ to polycyclic aromatic hydrocarbon-induced carcinogenesis.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D011817:Rabbits
D001580:Benzopyrenes; D005965:Glucuronates; D005982:Glutathione Transferase; D005966:Glucuronidase