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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.

The modulating effects of turmeric (T), ethanolic turmeric extract (ETE) and curcumin-free aqueous turmeric extract (CFATE) on the initiation or post-initiation phases of DMBA-induced mammary tumorigenesis were investigated in female Sprague-Dawley rats. Dietary administration of 1% T/0.05% ETE 2 weeks before, on the day of DMBA treatment (day 55) and 2 weeks after the single dose (15 mg/animal) of DMBA (during the initiation period) resulted in significant suppression of DMBA-induced mammary tumorigenesis as seen by a reduction in tumor multiplicity, tumor burden and tumor incidence. However, simultaneous administration of 1% T-derived CFATE as the sole source of drinking water during the initiation phase did not suppress DMBA-induced mammary tumorigenesis. Dietary administration of 1% T/0.05% ETE or 1% T-derived CFATE as the sole source of drinking water starting 48 h after DMBA treatment and continuing until the end of the experiment (during the post-initiation period) resulted in significant suppression of DMBA-induced mammary tumorigenesis as seen by reduction in the tumor multiplicity and/or tumor burden although tumor incidence was unaffected. The present data clearly indicate that dietary administration of T/ETE showed strong chemopreventive activity during initiation as well as post-initiation phases of DMBA-induced rat mammary tumorigenesis while CFATE was found to be weakly active only when it was administered during the post-initiation phase.

The modulating effects of curcumin-free aqueous turmeric extract (CFATE), ethanolic turmeric extract (ETE) and turmeric (T) powder on the benzo(a)pyrene (B(a)P)-induced forestomach tumors were investigated in Swiss female albino mice receiving oral administration of B(a)P at a dose of 1 mg twice weekly for 4 weeks. Administration of 0.2%/1.0%/5.0% turmeric-derived CFATE as sole source of drinking water or 0.01%/0.05%/0.25% ETE in diet or 0.2%/1.0%/5.0% T in diet, 2 weeks before, during and 2 weeks after the last dose of B(a)P (during initiation period) resulted in significant suppression of B(a)P-induced tumorigenesis when compared with the group receiving B(a)P and control diet/drinking water. Among different fractions tested, CFATE appears to be more powerful as not only did it reduce the tumor multiplicity to the lowest levels but it also significantly reduced the tumor incidence. Administration of 5.0% turmeric-derived CFATE as the sole source of drinking water or 0.25% ETE/5.0% T in diet starting from 48 h after the last dose of B(a)P (during the post-initiation period) until the termination of the experiment, also inhibited the formation of multiple gastric tumors by B(a)P, although the suppression of tumor multiplicity was appreciably more in the groups that received 5.0% turmeric-derived CFATE/0.25% ETE treatment during initiation with carcinogen, i.e. 2 weeks before, during and 2 weeks after the last dose of B(a)P. The present data clearly indicate the potential of turmeric-derived CFATE as a powerful chemopreventive fraction and also demonstrate the efficacy of lower, i.e. 1/25th and/or 1/5th of the reported, chemopreventive doses of T/ETE (essentially curcumins) in inhibiting B(a)P-induced forestomach tumors in mice.

The effects of turmeric (T), curcumins (Cs), aqueous turmeric extract (ATE) and curcumin-free aqueous turmeric extract (CFATE) on the formation of [3H]benzo[a]pyrene ([3H]B(a)P)-derived DNA adducts was studied in vitro employing mouse liver S9. A dose-dependent decrease in binding of [3H]B(a)P metabolites to calf thymus DNA was observed in the presence of T, Cs and ATE but not in the presence of CFATE, suggesting curcumins to be active principles. Further studies employing mouse liver microsomes and individual components of curcumins, i.e. curcumin (C), demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC) showed that all the three components brought about dose-dependent; inhibition of [3H]B(a)P-DNA adduct formation and inhibitory activity was in the order C > dmC > bdmC. Investigations on the inhibitory effect of curcumin showed a dose-dependent decrease in cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) activity resulting in relatively larger amounts of unmetabolized B(a)P in the presence of curcumin. Comparison of structures of curcumins with their activity profile suggested the importance of both parahydroxy (p-OH) and methoxy groups (-OCH3) in the structure activity relationship. Experiments to study the mechanism of action of curcumin indicated that the presence of curcumin was essential for the inhibitory effect, as removal of curcumin resulted in restoration of cytochrome P450 activity and the levels of [3H]-B(a)P-DNA adducts to control values. The present studies demonstrate that curcumin is effective in inhibiting [3H]B(a)P derived DNA adducts by interfering with the metabolic enzymes and its physical presence is essential for this effect.