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Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts
Rachana Thapliyal1, Shailesh S Deshpande, Girish B Maru
1Carcinogenesis Division, Cancer Research Institute, Tata Memorial Centre, Parel, 400 012, Mumbai, India.
Abstract:
The effects of turmeric feeding before and after benzo(a)pyrene [B(a)P] exposure on the levels of B(a)P-derived DNA adducts were studied in tissues of Swiss mice employing (32)P-postlabelling analysis. A reduction in the levels of B(a)P-derived DNA adducts in liver, lung, and forestomach was observed in animals pre-treated with 0.2 or 1% turmeric diet and exposed to B(a)P by oral intubation when compared to animals receiving standard laboratory diet and B(a)P. The observed decrease was not due to dilution caused by nascent DNA synthesis. Comparative evaluation of levels of B(a)P-derived DNA adducts in tissues of animals shifted to 0.2 or 1% turmeric diet after 24 h of oral intubation of B(a)P with those continued on standard laboratory diet did not suggest enhanced disappearance/repair of B(a)P-derived DNA adducts due to exposure to turmeric. Further, pre-treatment of mice with 1% turmeric diet significantly reduced the B(a)P-induced increase in activity of cytochrome P450 (CYP450) isozymes CYP 1A1 and 1A2 in liver, lung, and forestomach of mice. In addition, hepatic glutathione S-transferase (GST) was found to be elevated in turmeric pre-treated mice. Thus turmeric-mediated decrease in induction of phase-I enzymes in liver, lung, and forestomach of mice and enhancement of hepatic GST appear to play an important role in reducing the B(a)P-induced DNA damage in target and non-target tissues.
Insights
Turmeric pre-treatment significantly reduced benzo(a)pyrene [B(a)P]-induced DNA damage in mice by lowering B(a)P-DNA adducts. This effect is linked to reduced CYP450 activity and increased glutathione S-transferase (GST).
Area of Science:
- Biochemistry
- Toxicology
- Chemoprevention
Background:
- Benzo(a)pyrene [B(a)P] is a polycyclic aromatic hydrocarbon and a known carcinogen.
- DNA adducts formed by B(a)P are critical biomarkers of exposure and potential initiators of carcinogenesis.
- Turmeric, containing curcumin, has demonstrated chemopreventive properties in various studies.
Purpose of the Study:
- To investigate the effect of turmeric feeding on benzo(a)pyrene [B(a)P]-induced DNA adduct formation.
- To determine if turmeric influences the metabolism of B(a)P by examining key detoxification enzymes.
- To elucidate the role of turmeric in modulating DNA damage in response to B(a)P exposure.
Main Methods:
- Swiss mice were fed diets containing 0.2% or 1% turmeric before and after B(a)P exposure.
- (32)P-postlabelling analysis was employed to quantify B(a)P-derived DNA adducts in liver, lung, and forestomach tissues.
- Activity assays for cytochrome P450 (CYP450) isozymes (CYP 1A1, 1A2) and hepatic glutathione S-transferase (GST) were performed.
Main Results:
- Pre-treatment with turmeric significantly reduced B(a)P-DNA adduct levels in the liver, lung, and forestomach.
- Turmeric pre-treatment suppressed the B(a)P-induced increase in CYP 1A1 and 1A2 activity.
- Hepatic GST activity was significantly elevated in mice pre-treated with turmeric.
Conclusions:
- Dietary turmeric effectively reduces B(a)P-induced DNA damage, likely through modulation of xenobiotic metabolism.
- The chemopreventive effect of turmeric involves the downregulation of phase-I enzymes (CYP450) and upregulation of phase-II enzymes (GST).
- These findings highlight turmeric's potential as a dietary agent for mitigating carcinogen-induced DNA damage.