Humans Exposed To Polychlorinated-Biphenyls (Pcbs) And Polychlorinated Dibenzofurans (Pcdfs) Exhibit Increased Sce Frequencies In Lymphocytes When Incubated With Alpha-Naphthoflavone - Involvement Of Metabolic-Activation By P-450 Isozymes

Our studies have shown that human exposure to cigarette smoke and polychlorinated biphenyls and dibenzofurans confers an increased sensitivity of lymphocytes to form SCEs following in vitro exposure to α-naphthoflavone (ANF). Studies of ANF metabolism by uninduced, phenobarbital and TCDD induced microsomes demonstrate that TCDD induced microsomes efficiently metabolize ANF, and that cytochrome P-450c is the isozyme responsible for its metabolism. The clastogenic properties of ANF, following metabolism by TCDD induced rat liver microsomes were characterized in Chinese Hamster Ovary (CHO) cells and it was determined that ANF can produce increased SCEs, chromosomal aberrations, β-thioguanine resistant mutants and ANF-DNA adducts.