GENETIC ALTERATIONS DURING CARCINOGENESIS INDUCED BY ENVIRONMENTAL CARCINOGENS

点击翻译按钮获取中文摘要

2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) is a potent, and one of the most abundant car cinogens contained in cooked meat and fish. It induces colon and prostate cancers in male F344 rats, and mammary cancers in female ones. Genetic alter ations and mutational spectra of colon-cancer related genes, such as Apc, β-catenin and K-ras, in PhIP-induced colon carcers and aberrant crypt foci (ACFs) were investigated to assess the contribution of PhIP in human colon car cinogenesis. Immunohistochemical analysis revealed that almost all the colon cancers contained an increased amount of β-catenin protein in either cytoplasm or nucleus of the cells. However, only 8 cases out of 18 examined were demonstr ated to have mutations in either the Apc or β-catenin gene. The remaining 10 cases may have mutations in other genes, which are also involved in the Wnt-signaling pathway. In contrast, only one ACF had mutations in the β-catenin gene, which was a C to A transversion at codon 36 converting histidine (His) to aspar agine (Asn). Therefore, one can easily speculate two possiblities. One is that ACFs detected as late as experimental week 60, could be those that had escaped from oncogenic mutations in Apc or β-catenin genes. Alter natively, different subsets of genes were altered in ACFs induced by PhIP.To address this question, chronological studies should be conducted to clarify the biological relevance of ACF in PhIP-induced colon carcinogenesis