THE ROLE OF LIVER NUCLEI IN THE FORMATION OF DNA BINDING PRODUCTS FROM BENZO(a) PYRENE

Publisher Summary This chapter discusses the role of liver nuclei in the formation of DNA binding products from benzo(a)pyrene (BP). It is generally assumed that the metabolic activation of the parent compound to electrophilic species that can interact with DNA is an early and critical event in the mutagenic and carcinogenic effect of BP and related compounds. Such electrophilic metabolites are produced by monooxygenation through the cytochrome P-450 system and include both primary epoxides and dihydrodiol epoxides. The nuclear BP monooxygenase can convert BP, and metabolites of BP preformed in the microsomes, to DNA binding products. A direct transfer of electrophilic microsomal metabolites seems to have contributed to the total incorporation of BP products into nuclear DNA. The relative importance of these mechanisms under physiological conditions remains to be established although it is tempting to speculate that the formation of the DNA binding species in the close vicinity of the nucleus would permit them to escape trapping by the various cytoplasmic defense systems and thus facilitate their binding to DNA.