Effect of UDP-glucuronic acid on the microsome-mediated binding of benzo(a)pyrene metabolites to calf thymus DNA

Abstract

The binding of benzo(a)pyrene (BP) to DNA in the presence of liver microsomal preparations from 3-methylcholanthrene-treated rats was increased 28.5% (P < 0.001) by addition of UDP-glucuronic acid to the incubation mixture at a 100 microM concentration of BP. However this increase was not observed at lower concentrations of BP. Analysis of DNA-hydrolysates by column chromatography on Sephadex LH-20 indicated that this increase was due to greater binding of benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. The amount of bound adducts derived from 9-hydroxybenzo(a)pyrene (9-OH BP) was not significantly affected by UDP-glucuronic acid. Addition of UDP-glucuronic acid to incubation mixtures containing microsomes from untreated rat liver caused only a slight increase in total binding. These findings suggest that UDP-glucuronyl transferase may be involved in the activation of BP.