Effects of curcumin on the formation of benzo[a]pyrene derived DNA adducts in vitro.

Abstract

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.