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[Effect of polychlorinated biphenyls on DNA damage induced by benzo[a]pyrene in HepG2 cells]
Wei Wei1, Chi Zhang, Ruiping Lai
1Department of Occupational and Environmental Health, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Objective:
To explore effects of polychlorinated biphenyl, PCB153 on DNA damage induced by benzo(a) pyrene (B[a]P) in HepG2 cells.
Methods:
As target cell, HepG2 cells were treated at the concentrations of 0.1, 1, 10 and 100 micromol/L with PCB153 and at the concentrations of 12.5, 25, 50 and 100 micromol/L B[a]P respectively. DMSO was used as solvent control. Single cell gel electrophoresis (SCGE) was applied for quantitative analysis of DNA damage which was caused by treating alone or co-treating with PCB153 and B[a]P, CYP1A1 (EROD) and CYP2B1 (PROD) activities were detected by using fluorescence spectrophotometry.
Results:
When compared with the solvent control, the DNA oliver tail moments were increased significantly (P < 0.01) in HepG2 cells treated with all the concentrations of B[a]P, while no significant DNA damage was observed in HepG2 cells treated with all the concentrations of PCB153. When compared with B[a]P treated alone, the DNA oliver tail moments showed a increase tendency in HepG2 cells co-treated with PCB153 (0.1, 1, 10 micromol/L) and B[a]P (50 micromol/L). But DNA oliver tail moments were increased significantly only when co-treated with 10 micromol/L of PCB153 and 50 micromol/L of B[a]P (P <0.01), while decreased significantly after co-exposuring to 100 micromol/L of PCB153 and 50 micromol/L of B[a]P (P <0.01). All concentrations of PCB153 induced significant increase in EROD and PROD activities in HepG2 cells.
Conclusion:
It was suggested that the enhancement of DNA damage induced by B[a]P could be associated with the increases of CYP1A1 and CYP2B1 activities induced by PCB153 in HepG2 cells.
Insights
Polychlorinated biphenyl (PCB153) exposure enhanced benzo(a)pyrene (B[a]P)-induced DNA damage in HepG2 cells by increasing CYP1A1 and CYP2B1 enzyme activities. However, high PCB153 concentrations reduced this DNA damage, suggesting a complex interaction.
Area of Science:
- Environmental Toxicology
- Molecular Toxicology
- Cell Biology
Context:
- Polychlorinated biphenyls (PCBs) are persistent environmental pollutants with known toxic effects.
- Benzo(a)pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a known carcinogen.
- HepG2 cells are a human liver cell line commonly used in toxicology studies.
Purpose:
- To investigate the effects of PCB153 on B[a]P-induced DNA damage in HepG2 cells.
- To determine the role of cytochrome P450 enzymes (CYP1A1 and CYP2B1) in mediating these effects.
Summary:
- B[a]P significantly increased DNA damage in HepG2 cells, while PCB153 alone did not.
- Co-exposure to PCB153 and B[a]P generally enhanced DNA damage, particularly at specific concentrations.
- PCB153 significantly increased CYP1A1 (EROD) and CYP2B1 (PROD) activities, suggesting a mechanism for enhanced DNA damage.
Impact:
- PCB153 can modulate the genotoxicity of B[a]P in liver cells.
- The induction of CYP enzymes by PCB153 plays a role in the combined toxicity of these chemicals.
- Findings contribute to understanding the complex interactions of environmental pollutants and their impact on cellular DNA.
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