Oxidative biotransformation of benzo(a)pyrene by human lung microsomal fractions prepared from surgical specimens.
1. Microsomal fractions were prepared from 15--50 g specimens of human lung tissue (mostly alveolar) obtained at surgical resections of 13 middle-aged male patients suffering from different pulmonary tumours. Marker enzyme assays indicated that the frations contained about 25% of the endoplasmic reticulum of the homogenate and about 10% of its mitochondrial membranes. 2. The content of cytochrome b5 corresponded to that of rodent lung microsomes, whereas the apparent content of cytochrom P-450 was much lower. 3. The extent of benzo(a)pyrene metabolism varied 13-fold between individuals in the group and was not detectable in about 40% of the cases. 4. The dihydrodiols as % of total metabolites formed was higher than in laboratory animals, the 7,8-dihydrodiol in most cases amounting to more than 40% of total dihydrodiols. 5. The apparent rate of hydroxylation was stimulated by 1 mM 2-diethylaminothyl 2,2-diphenylvalerate and by 1 mM 1,2-oxy-3,3,3-trichloropropane, but inhibited moderately by 0.1 mM metyrapone and extensively by 0.05 mM 7,8-benzoflavone. 6. Ethoxyresorufin deethylation qualitatively paralleled benzo(a)pyrene hydroxylation among individuals.
D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D010084:Oxidation-Reduction
D001580:Benzopyrenes; D001579:Benzopyrene Hydroxylase