Tumor promotion by fecapentaene-12 in a rat colon carcinogenesis model

Fecapentaenes are a group of fecal mutagens produced by anaerobicmicroflora of the colon. The potential of fecapentaene-12 (FP-12)to promote tumor development was tested in a rat colon carcinogenesismodel using N-methyl-N-nitrosourea (MNU) as the initiating agent.Two groups of female F-344 rats were initiated by intrarectalinstillations of MNU (2 mg in 0.5 ml H₂O, 3 times a week, for3 weeks; MNU and MNU + FP-12 groups). Two additional groups(FP-12 and Control) were given H₂O without carcinogen. In thepost-initiation phase, rats of the MNU + FP-12 and FP-12 groupswere intrarectally administered 400 ng of FP-12 in 0.5 ml T-Ebuffer, twice a week, for 24 weeks, whereas the MNU and Controlgroups received the vehicle only. Tumors were found only inthe MNU and MNU + FP-12 groups, their number being higher inthe latter. The number of carcinoma bearing rats as well asthe average number of carcinomas per rat were significantlyhigher (P< 0.05) in the MNU + FP-12 group as compared tothe MNU-alone values. Aberrant crypt foci (ACF) were found inall carcinogen-treated rats, including those that did not containtumors, whereas none were observed in the FP-12 and Controlgroups. The average number of ACF/cm² was also significantlyhigher in the MNU + FP-12 group, as was the case for the averagenumber of ACF containing >10 aberrant crypts per focus. Thesefindings suggest that FP-12 can express promoting activity inchemically induced colon carcinogenesis.