Oxidative Biotransformation of Benzo(a)Pyrene by Human Lung Microsomal Fractions Prepared from Surgical Specimens

Abstract

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 fractions 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 cytochrome 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.