Effects of activation of UDP-glucuronyl transferase on metabolism of benzo(a)pyrene with rat liver microsomes.

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Abstract
The effects of Brij 58 on microsome-mediated benzo[a]pyrene (BP)[a carcinogen]-metabolism were investigated. At a concentration of 0.01%, which did not decompose the microsomal mixed-function oxidase system, Brij 58 increased UDP-glucuronyl transferase activity on 3-hydroxy-BP to 560% of the control level. Quantitative changes of BP-metabolites by glucuronidation were found by high performance liquid chromatography. On incubation in the presence of UDP-glucuronic acid, the amounts of phenols decreased but the amounts of dihydrodiols did not change. Brij 58 enhanced the decrease in phenol metabolites. The binding of BP-metabolites to DNA was higher in the presence of UDP-glucuronic acid, and Brij 58 also enhanced the binding in the presence of UDP-glucuronic acid. The ratio of bound adducts with BP-7,8-dihydrodiol-9,10-oxide to those with 9-hydroxy-BP-4,5-oxide, which were separated by Sephadex LH-20 column chromatography, was increased by UDP-glucuronic acid and further enhanced by Brij 58. These results are discussed in relation to the role of glucuronidation in BP metabolism.

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