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Published on: March 20, 2018
[Protective action of biphenyl dimethyl dicarboxylate (DDB) against liver nuclear DNA damage induced by carcinogens]
Abstract:
The protective effect of DDB against carcinogen-induced DNA damage was examined in the present investigation. Preincubation of rat liver nuclei with DDB (1 mmol/L) resulted in inhibition of binding of 3H-benzo (a) pyrene to nuclear DNA. The inhibition rate was about 60%. Unscheduled DNA synthesis (UDS) of freshly isolated rat hepatocytes induced by aflatoxin B1 (10(-7) mol/L) was also dose dependently inhibited by DDB (10(-6)-10(-3) mol/L). Oral administration of DDB at 200 mg/kg once daily for 3 days was effective to induce increase of liver cytosol glutathione-S-transferase and microsomal UDPG-transferase in mice. The results indicate that DDB is able directly or indirectly to antagonize certain carcinogen-induced DNA damages.
Insights
DDB demonstrates protective effects against carcinogen-induced DNA damage by inhibiting benzo(a)pyrene binding and aflatoxin B1-induced DNA synthesis. It also enhances protective enzymes in mice.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Context:
- Carcinogen exposure poses significant health risks due to DNA damage.
- Understanding protective mechanisms against carcinogens is crucial for developing preventative strategies.
- Benzo(a)pyrene and aflatoxin B1 are known potent carcinogens that induce DNA damage.
Purpose:
- To investigate the protective effects of DDB against carcinogen-induced DNA damage.
- To determine DDB's impact on the binding of benzo(a)pyrene to DNA.
- To evaluate DDB's inhibition of unscheduled DNA synthesis (UDS) induced by aflatoxin B1.
- To assess DDB's effect on the activity of liver enzymes involved in detoxification.
Summary:
- DDB (1 mmol/L) inhibited the binding of 3H-benzo(a)pyrene to rat liver nuclear DNA by approximately 60%.
- DDB dose-dependently inhibited aflatoxin B1-induced UDS in rat hepatocytes.
- Oral administration of DDB (200 mg/kg) increased liver cytosol glutathione-S-transferase and microsomal UDP-glucuronosyltransferase activity in mice.
Impact:
- DDB exhibits direct and indirect mechanisms to counteract carcinogen-induced DNA damage.
- These findings suggest DDB's potential as a chemopreventive agent.
- The study highlights DDB's role in enhancing the body's natural detoxification pathways.
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