Though phase II enzymes catalyze the detoxification PF-01367338 of BPDE, some of the reactive electrophiles interact
covalently with DNA to form adducts that mark an early initiation event. Unrepaired/misrepaired adducts lead to mutation in genes involved in proliferation, growth, apoptosis and finally to a disease condition such as cancer [4]. Plant-derived natural compounds have been receiving increased attention as chemopreventives because of their low toxicity and high tolerability. The efficacy of polyphenols when administered before or after the carcinogen treatment has been established and shown to modulate carcinogen-induced incidence/multiplicity/latency period of tumor development [5]. Curcumin/turmeric has been shown to possess chemopreventive activity at both initiation and promotion stages of chemical-induced carcinogenesis ([6], [7], [8], [9] and [10]). Earlier studies have shown that dietary curcumin pre-treatment decreases the formation of B(a)P-derived DNA adducts in mouse tissues by inhibiting carcinogen-induced phase I enzymes and directly Selleck SGI-1776 inducing
phase II enzymes [7]. Effects of turmeric/curcumin after exposure to carcinogens on the repair or disappearance of adducts, if any, are not known. Hence, in the present study, the post-treatment effect of curcumin on the disappearance of BPDE-DNA adducts in tissues of mice have been evaluated. Herein, we show that dietary curcumin treatment subsequent to B(a)P exposure enhances the disappearance of BPDE-DNA adducts. This could possibly be due to the curcumin-mediated enhancement of apoptosis of DNA adduct-containing selleck products cells
and/or repair of DNA-adducts in mouse tissues. Benzo(a)pyrene [B(a)P] (purity ∼98%) and curcumin (purity ∼65-70%) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Antibodies for Bax, Bcl-2, cyclin D1, β-actin, anti-mouse horseradish peroxidase (HRP) conjugated secondary antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and caspase-3 from Abcam (Cambridge, MA, USA). Monoclonal antibody for BPDE-DNA adduct clone 5D11 was obtained from Hycult Biotechnology (Uden, Netherlands). The monoclonal antibody for proliferating cell nuclear antigen (PCNA) was procured from BD Pharmingen (San Diego, CA, USA). The anti-rabbit HRP conjugated secondary antibodies were obtained from Amersham Biosciences (Buckinghamshire, UK). All animal studies were conducted with approval from the Institutional Animal Ethics Committee endorsed by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India guidelines.