Analysis of Multistep Colon Carcinogenesis

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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant mutagenic and carcinogenic heterocyclic amines produced by the cooking of meat and fish [Sugimura et al., Nakagama et al.]. We analyzed multistep colon carcinogenesis induced by PhIP using a rat model. A subset of ACF induced by PhIP, especially dysplastic ones, is considered to develop to high grade dysplastic ACF, adenocarcinomas and invasive adenocarcinomas [Ochiai et al., Nakagama et al.]. Staphylococcal nuclease domain containing 1 (Snd1) was recently reported to be a component of RNA-induced silencing complex (RISC), which is related to post-transcriptional control of gene expression. Accumulation of Snd1 was detected in some ACF and may participate in early steps in colon carcinogenesis [Tsuchiya et al.]. Also, we investigated genetic susceptibility to the induction of colon cancers, especially related to early steps in colon carcinogenesis using the strain differences of rats in ACF induction. In colon cancers, most of them harbor mutations of either the Apc or β-catenin gene [Dashwood et al., Ubagai et al.] and manifest gene expression profiles similar to those of human colon cancers [Fujiwara et al.]. Now the aberrations of genome structure in colon cancers are also being analyzed using array-comparative genomic hybridization (CGH).


Multistep colon carcinogenesis of rats induced by PhIP