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The Benzo(a)pyrene Deoxyribonucleoside Products Isolated from DNA after Metabolism of Benzo(a)pyrene by Rat Liver Microsomes in the Presence of DNA¹

Chemical Carcinogenesis Division, Institute of Cancer Research, Pollards Wood Research Station, Nightingales Lane, Chalfont St. Giles, Buckinghamshire HP8 4SP, United Kingdom

Rat liver microsomes (induced by 3-methylcholanthrene) were used to catalyze the binding of tritium-labeled benzo(a)pyrene to DNA. Enzymic degradation of this DNA to deoxyribonucleosides, followed by separation of the products by Sephadex LH20 column chromatography, revealed two major products. One of these was shown to be the same as that obtained from DNA with benzo(a)pyrene bound following treatment of mouse embryo cells in culture with the carcinogen. Neither product resembled those obtained from DNA that had been caused to react with benzo(a)pyrene 4,5-oxide (K-region epoxide). The aryl hydrocarbon hydroxylase activity of the microsome preparations was determined and related to the extent of microsome-catalyzed hydrocarbon binding. Inhibitors of the enzyme epoxide hydrase increased this binding but caused the loss of one of the two major products. On the basis of the results obtained, a model is proposed of the mechanism of benzo(a)pyrene metabolism and DNA binding.

¹ This work was supported by NIH Contract NO1-CP-33367 and in part by grants to the Chester Beatty Research Institute from the Medical Research Council and the Cancer Research Campaign.

Received 10/ 8/74. Accepted 1/30/75.