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 3H-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 Bcl2 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.
Garg
Rachana
R
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai-410 208, India.
Maru
Girish
G
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D018736:DNA Adducts / Q000032:analysis*; D004032:Diet; D008297:Male; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D018736:DNA Adducts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D011494:Protein Kinases; D053148:Caspase 3; D003474:Curcumin