Effect of smoking on benzo(a)pyrene metabolism by human placental microsomes

Abstract

Placentas were collected at term from a series of 21 women. Thirteen were smokers, and eight were nonsmokers. Microsomes were prepared and used in the following studies of benzo(a)pyrene metabolism: aryl hydrocarbon, hydroxylase, epoxide hydrase, high-pressure liquid chromatographic analysis of benzo(a)pyrene metabolites, and DNA binding. DNA-binding adducts were further characterized by Sephadex LH-20 chromatography. Aryl hydrocarbon hydroxylase activity was much higher in smokers than in nonsmokers. Epoxide hydrase activity with styrene oxide as the substrate showed no difference between smokers and nonsmokers. High-pressure liquid chromatographic analysis showed much greater formation of dihydrodiols, quinones, and phenols by microsomes from smokers. The amount of benzo(a)pyrene-7,8-dihydrodiol was almost equal to the amount of phenols produced by the microsomes of the smokers. Sephadex LH-20 analysis of DNA binding resulted in only one major benzo(a)pyrene-DNA adduct when microsomes from smokers were used; this peak corresponds to benzo(a)pyrene 7,8-diol-9, 10-oxide bound to DNA nucleoside(s).