Abstract
The metabolism of benzo(a)pyrene by isolated perfused lungs and tracheal, bronchial and lung cultures has been studied in both rats and hamsters. The ethyl acetate-soluble metabolites from the medium are qualitatively similar in the tracheal and bronchial cultures, whereas, in the lung cultures large amounts of a new metabolite (X) derived from 3-hydroxybenzo(a)pyrene are formed. An unidentified metabolite (Y) migrating between 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene was observed in rat and hamster lung cultures and isolated rat lung perfusions. Dihydrodiols, in particular 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, are the major metabolites formed in the tracheal and bronchial cultures. In contrast to this 3-hydroxybenzo(a)pyrene and a metabolite derived from it (X) are the major metabolites formed by the isolated perfused lungs and lung cultures respectively. In the lung cultures much higher concentrations of water-soluble metabolites are produced than in the tracheal and bronchial cultures. The formation, accumulation and relative resistance to metabolism to water-soluble metabolites of dihydrodiols in the trachea and bronchi may partially explain the higher susceptibility of these areas to hydrocarbon carcinogenesis compared to the lungs.
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