Tumor promotion by fecapentaene-12 in a rat colon carcinogenesis model.
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 chemical induced colon carcinogenesis.
Zarkovic
M
M
Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.
Qin
X
X
Nakatsuru
Y
Y
Oda
H
H
Nakamura
T
T
Shamsuddin
A M
AM
Ishikawa
T
T
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008770:Methylnitrosourea / Q000633:toxicity; D011090:Polyenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D011090:Polyenes; D008770:Methylnitrosourea; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene