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© 1993 Oxford University Press

research-article

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

Mirjana Zarkovic, Xiusheng Qin, Yoko Nakatsuru, Hideaki Oda, Takuro Nakamura, Abulkalam M. Shamsuddin 1 and Takatoshi Ishikawa 2

Department of Pathology, Faculty of Medicine, University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan
1Department of Pathology, University of Maryland School of Medicine MD 21201, USA

2To whom reprint requests should be sent

Fecapentaenes are a group of fecal mutagens produced by anaerobic microflora of the colon. The potential of fecapentaene-12 (FP-12) to promote tumor development was tested in a rat colon carcinogenesis model using N-methyl-N-nitrosourea (MNU) as the initiating agent. Two groups of female F-344 rats were initiated by intrarectal instillations of MNU (2 mg in 0.5 ml H2O, 3 times a week, for 3 weeks; MNU and MNU + FP-12 groups). Two additional groups (FP-12 and Control) were given H2O without carcinogen. In the post-initiation phase, rats of the MNU + FP-12 and FP-12 groups were intrarectally administered 400 ng of FP-12 in 0.5 ml T-E buffer, twice a week, for 24 weeks, whereas the MNU and Control groups received the vehicle only. Tumors were found only in the MNU and MNU + FP-12 groups, their number being higher in the latter. The number of carcinoma bearing rats as well as the average number of carcinomas per rat were significantly higher (P< 0.05) in the MNU + FP-12 group as compared to the MNU-alone values. Aberrant crypt foci (ACF) were found in all carcinogen-treated rats, including those that did not contain tumors, whereas none were observed in the FP-12 and Control groups. The average number of ACF/cm2 was also significantly higher in the MNU + FP-12 group, as was the case for the average number of ACF containing >10 aberrant crypts per focus. These findings suggest that FP-12 can express promoting activity in chemically induced colon carcinogenesis.


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