Metabolism and covalent binding of benzo[alpha]pyrene in human peripheral lung

Short-term organ cultures of peripheral lung from lung cancer patients metabolise benzo[alpha]pyrene to ethylacetate-soluble metabolites, which covalently bind to tissue macromolecules. The nature and quantities of metabolites formed and the extent of covalent binding are dependent upon the time of incubation, the substrate concentration and interindividual variability in the metabolic activity of the lung. Individuals whose lungs rapidly metabolise the carcinogen exhibit more extensive further metabolism of primary metabolites and higher levels of covalent binding. Certain striking differences in the relative retention in the tissue or release into the extra-cellular medium of different metabolites have been found as illustrated by the observation that the ratio of 7,8-dihydro-7,8-dihydroxybenzo[alpha]-pyrene to 9,10-dihydro-9,10-dihydroxybenzo[alpha]pyrene was always significantly higher in the tissue than in the extracellular medium.