EFFECTS OF CURCUMIN ON THE FORMATION OF BENZO[ALPHA]PYRENE DERIVED DNA-ADDUCTS IN-VITRO

The effects of turmeric (T), curcumins (Cs), aqueous turmeric extract (ATE) and curcumin-free aqueous turmeric extract (CFATE) on the format ion of [H-3]benzo[a]pyrene ([H-3]B(a)P)-derived DNA adducts was studie d in vitro employing mouse liver S9. A dose-dependent decrease in bind ing of [H-3]B(a)P metabolites to calf thymus DNA was observed in the p resence of T, Cs and ATE but not in the presence of CFATE, suggesting curcumins to be active principles. Further studies employing mouse liv er microsomes and individual components of curcumins, i.e. curcumin (C ), demethoxycurcumin (dmC) and bis-demethoxycurcumin (bdmC) showed tha t all the three components brought about dose-dependent; inhibition of [H-3]B(a)P-DNA adduct formation and inhibitory activity was in the or der C > dmC > bdmC, investigations on the inhibitory effect of curcumi n showed a dose-dependent decrease in cytochrome P450 and aryl hydroca rbon hydroxylase (AHH) activity resulting in relatively larger amounts of unmetabolized B(a)P in the presence of curcumin. Comparison of str uctures of curcumins with their activity profile suggested the importa nce of both parahydroxy (p-OH) and methoxy groups (-OCH3) in the struc ture activity relationship. Experiments to study the mechanism of acti on of curcumin indicated that the presence of curcumin was essential f or the inhibitory effect, as removal of curcumin resulted in restorati on of cytochrome P450 activity and the levels of [H-3]-B(a)P-DNA adduc ts to control values. The present studies demonstrate that curcumin is effective in inhibiting [H-3]B(a)P derived DNA adducts by interfering with the metabolic enzymes and its physical presence is essential for this effect.