Antimutagenicity and chemopreventive ability of 80% ethanolic extract of bitter melon (Momordica charantia) was investigated. The Momordica charantia extract is nonmutagenic, but inhibits the mutagenicity of Glu-P-2, IQ, MeIQ, MeIQx, PhIP and AFB1 in the Salmonella mutation pre-incubation technique. The ability of Momordica charantia extract to inhibit colon carcinogenesis was conducted in Male F344 rats, using azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) and DNA adduct formation as biomarkers. Rats were fed daily with various concentrations of Momordica charantia extract at 0.1 and 1.0 g/kg body weight (bw)by gavage for 2 and 5 weeks to study DNA adduct and ACF at initiation stage, respectively. One week after the administration of the plant extract, rats were subcutaneously injected with AOM at 15 mg/kg bw subcutaneously for two weeks apart (Day 7 and 14). Three rats of each group were sacrificed 12 h. after the second AOM injection, and DNA was extracted from the colon. DNA adduct formations

O6-methylguanine (O6-meGua) and N7-methylguanine (N7-meGua) were analyzed by HPLC. Remained rats were sacrificed 3 weeks after the second AOM injection and ACF formation at initiation stage was examined. To study antitumor formation of Momordica charantia extract at the promotion step, rats were fed with Momordica charantia extract at 0.1 and 1.0 g/kg bw 2 weeks after the second AOM injection and continued for 12 weeks. All rats were sacrificed after 12 weeks and ACF formations in colonic mucosa were examined. The results showed that the decrease of O6-meGua and N7-meGua adduct levels in colonic mucosa and colonic muscular in rats received Momordica charantia extract was not different from control rats. At initiation stage, treatment with Momordica charantia extract at 1.0 and 0.1 g/kg bw, significantly inhibited total ACF formation 21% and 18%, respectively. At promotion stage, Momordica charantia extract at 1.0 g/kg bw, significantly inhibited ACF formation 18%. In addition, Momordica charantia extract also decreased the formation of larger ACF with more than 4 crypts/focus, which correlated with tumor incidence, as high as 41%. To explain the possibility of a protective mechanism of Momordica charantia extract against colon carcinogenesis, the effect of Momordica charantia extract on bacterial b-glucuronidase activity (in vitro) was also investigated. The results showed that Momordica charantia extract mildly inhibited bacterial b-glucuronidase activity. It is suggested that Momordica charantia extract weakly inhibited the release of free MAM from MAM-glucuronide in the colon, leading to DNA adduct formation and consistent with the weakly inhibitory effect of Momordica charantia extract on ACF formation at initiation stage (inhibitory effect less than 40%). Interestingly, Momordica charantia extract has inhibitory effect on ACF with more than 4 crypts/focus at promotion stage. However, the exact mechanism of this effect can not explain by this investigation. In summary, Momordica charantia extract shows a tendency to prevent colon carcinogenesis at promotion stage, not at initiation stage, The extract did not inhibited O6-meGua adduct formation which is considered to be a critical step for initiation of carcinogenesis. Although, the exact mechanism of the chemopreventive effects of Momordica charantia are not yet known, the results described here suggest a possibility of chemopreventive action of Momordica charantia extract against colon cancer in rat model by exerting specific effect on promotion stage.