BENZO(A)PYRENE OXIDATION, CONJUGATION AND DISPOSITION IN THE ISOLATED PERFUSED RABBIT LUNG - ROLE OF THE GLUTATHIONE S-TRANSFERASES

  • 1 January 1979
    • journal article
    • research article
    • Vol. 57  (5) , 298-305
Abstract
The isolated perfused rabbit lung metabolized 7-11% of 20 .mu.mol 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%. Of the water-soluble metabolites (40%) were chromatographically identical to the glutathione conjugate or benzo(a)pyrene 4,5-oxide. Sulfate 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 sulfuric 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.