The benzo(alpha)pyrene deoxyribonucleoside products isolated from DNA after metabolism of benzo(alpha)pyrene by rat liver microsomes in the presence of DNA.
Rat liver microsomes (induced by 3-methylcholanthrene) were used to catalyze the binding of tritium-labeled benzo(alpha)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(alpha)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(alpha)pyrene 4,5-oxide (K-region eposide). 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(alpha)pyrene metabolism and DNA binding.
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001580:Benzopyrenes / Q000302:isolation & purification* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000302:isolation & purification* / Q000378:metabolism; D004852:Epoxy Compounds; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding
D001580:Benzopyrenes; D003853:Deoxyribonucleosides; D004852:Epoxy Compounds; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; D006836:Hydro-Lyases