EFFECTS OF DIFFERENT CELL CONSTITUENTS ON METABOLIC-ACTIVATION AND BINDING OF BENZO (ALPHA) PYRENE TO PURIFIED AND NUCLEAR-DNA

The binding of metabolites of 9-hydroxybenzo(a)pyrene and 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene [potential carcinogen] to DNA was compared in various incubation systems. The total binding was greatest when a system of purified DNA and liver microsomes was used. In this system the major binding species was derived from 9-hydroxybenzo(a)pyrene. When systems employing liver nuclei supplemented with microsomes, albumin or cytosol were used, the total binding to DNA was much lower and species derived from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene predominated. Binding in the purified system correlated poorly with binding in the nuclear system and the majority of microsomally produced benzo(a)pyrene electrophiles may never reach the nucleus due to trapping by cytoplasmic nucleophiles. Nuclear metabolism may play an important role in the binding of benzo(a)pyrene to DNA in vivo.