Influence of Aroclor 1254 on Benzo(a)Pyrene-Induced DNA Breakage, Oxidative DNA Damage, and Cytochrome P4501A Activity in Human Hepatoma Cell Line

摘要

Both polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are important environmental pollutants. They coexist widely in the environment at very low levels. Numerous studies indicated that aroclor1254 (one of PCBs mixture) is the inducer of cytochrome P450 1A enzyme acitivity. Benzo(a)pyrene (BaP) can cause a variety of toxicities in vitro, such as oxidative DNA damage and genotoxicity. In the present study, HepG2 cells were treated with either BaP (50 μM) or arocior1254 at concentrations of 11.5 (low), 23.0 (medium), and 46.0 μM (high) alone, or pretreated the cells with aro-clor1254 (11.5, 23.0, and 46.0 μM), followed by BaP (50 μM). It was found that 7-ethoxyresorufin-O-deety-lase (EROD) activities of HepG2 cells exposed to either BaP or aroclor 1254 increased. DNA damage measured by DNA migration and the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) also increased in cells exposed to BaP, but not in cells exposed to aroclor1254. Under the Aroclor 1254 pretreatment condition, BaP-induced EROD activities was enhanced in cells exposed to the medium and high concentrations of aroclor1254 (P < 0.01 for both), whereas in all pretreatment groups aroclor1254 significantly increased BaP-induced DNA migration (P < 0.01 for all) and the 8-OHdG formation (P < 0.05 for all). In addition, there was positive correlation between the EROD induction activity and Olive tail moment (r~2 = 0.958, P < 0.01) or the levels of 8-OHdG (r~2 = 0.992, P < 0.01). The findings suggest that under the experimental conditions aroclor1254 may enhance BaP-induced DNA migration and oxidative DNA damage inrnHepG2, due to inducing CYP1A enzyme activity.