Zarkovic M, Qin X, Nakatsuru Y, Oda H, Nakamura T, Shamsuddin A M, Ishikawa T
Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.
Carcinogenesis. 1993 Jul;14(7):1261-4. doi: 10.1093/carcin/14.7.1261.
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.
粪五烯是由结肠厌氧微生物群产生的一组粪便诱变剂。在以N-甲基-N-亚硝基脲(MNU)作为引发剂的大鼠结肠癌发生模型中,测试了粪五烯-12(FP-12)促进肿瘤发展的潜力。两组雌性F-344大鼠通过直肠内注入MNU(0.5 ml水中含2 mg,每周3次,共3周;MNU组和MNU + FP-12组)进行引发。另外两组(FP-12组和对照组)给予不含致癌物的水。在引发后阶段,MNU + FP-12组和FP-12组的大鼠每周两次经直肠给予0.5 ml T-E缓冲液中含400 ng的FP-12,共24周,而MNU组和对照组仅接受赋形剂。仅在MNU组和MNU + FP-12组中发现肿瘤,后者的肿瘤数量更多。与单独使用MNU组相比,MNU + FP-12组中患癌大鼠的数量以及每只大鼠的癌平均数量显著更高(P < 0.05)。在所有经致癌物处理的大鼠中,包括那些未发生肿瘤的大鼠,均发现了异常隐窝灶(ACF),而在FP-12组和对照组中未观察到。MNU + FP-12组中每平方厘米ACF的平均数量也显著更高,每个病灶中含有> 10个异常隐窝的ACF平均数量也是如此。这些发现表明,FP-12在化学诱导的结肠癌发生中可表现出促进活性。