Dietary Curcumin Enhances Benzo(a)pyrene-Induced Apoptosis Resulting in a Decrease in BPDE-DNA Adducts in Mice

Curcumin pretreatment has been shown to decrease the formation of B(a)P-derived DNA adducts; however, its effects on disappearance of BPDE-DNA adducts in vivo remain unexplored. We investigate the effect of curcumin on persistence of BPDE-DNA adducts and cell turnover in mouse tissues. Mice administered 1 mg B(a)P (gavage) were randomized after 24 h into group A (sacrificed at zero time), group B (continued on control diet), and group C (shifted to 0.05% curcumin diet), and sacrificed after 24, 48, and 96 h. Compared to group A, a time-dependent decrease in DNA adducts was observed in liver/lungs of group B mice. Mice shifted to curcumin diet showed a relatively higher decrease in DNA adducts when compared to group A/time-matched controls (group B). To investigate if this enhanced decrease was due to dilution by newly synthesized DNA or due to cell turnover; rate of DNA synthesis and apoptosis were evaluated. Similar levels of H-3-thymidine incorporated in tissue DNA from group B/C ruled out the possibility of adduct dilution. Comparative evaluation of apoptosis-related parameters showed increased apoptotic-index, p53, Bax and Caspase-3 protein expression and decreased Bc12 levels in group C than in group A/B. This implies that curcumin post-treatment augments apoptosis of adducted cells resulting in enhanced decrease in DNA adducts.