Influence of aroclor 1254 on benzo(a)pyrene‐induced DNA breakage, oxidative DNA damage, and cytochrome P4501A activity in human hepatoma cell line

Abstract

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 microM) or aroclor1254 at concentrations of 11.5 (low), 23.0 (medium), and 46.0 microM (high) alone, or pretreated the cells with aroclor1254 (11.5, 23.0, and 46.0 microM), followed by BaP (50 microM). It was found that 7-ethoxyresorufin-O-deetylase (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 in HepG2, due to inducing CYP1A enzyme activity.

Triclosan reduces the levels of global DNA methylation in HepG2 cells

“…Furthermore, TCS treatment promoted the accumulation of 8-OHdG in the genomic DNA, but reduced the relative levels of MBD2, MBD3, and MeCP2 mRNA transcripts in HepG2 cells. We used HPLC-MS/MS for quantification of the levels of GDM and 8-OHdG and found that the levels of GDM and 8-OHdG in un-treated HepG2 cells were similar to that in other reports Aniagu et al, 2009;Yuan et al, 2009), validating the sensitivity of our experimetnal system. Furthermore, treatment with a DNA methylation inhibitor of AZA greatly decreased the GDM level, while treatment with NAC significantly mitigated TCS-induced accumulation of 8-OHdG in genomic DNA, both of which further validated the accuracy of this method.…”

LINE-1 gene hypomethylation and p16 gene hypermethylation in HepG2 cells induced by low-dose and long-term triclosan exposure: The role of hydroxyl group

“…E) The structures of TCS and MTCS. Control cells were treated with 0.1% DMSO (v/v) level of 8-OHdG levels in HepG2 cells was 2.3/10 6 dG, which was similar to the reported data by Yuan et al (2009). After treated with low-dose TCS, 8-OHdG levels significantly increased (p b 0.01) compared with the control group (Fig.…”

Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats

“…PCBs enhanced CYP450 activities in animals [21, 22]. By MTT and Western blot methods, our results proved that the expression of CYP450 increased gradually with the treatment of the gradient Aroclor 1254; the highest expression was observed under 1  μ g/mL Aroclor 1254 treatment.…”