酸化ストレス発がんの分子機構とその標的遺伝子 : 第12回公開シンポジウム : 活性酸素の分子病態学

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Oxidative stress has been associated with carcinogenesis. In 1982, our laboratory established an oxys-tress-induced carcinogenesis model of rodent kidney by the use of an iron chelate, ferric nitrilotriacetate. This model is unique in that 1) only carcinoma, not sarcoma, is induced, 2) the induced tumor is of high malignant potential to kill the animal by pulmonary metastasis, peritoneal invasion or rupture of the primary tumor, and, 3) increase in a variety of covalently modified products including 8-oxoguanine, thymine-tyrosine cross-link, 4-hydroxy-2-nonenal and its modified proteins are demonstrated in its early stage. Since in general free radicals are not considered to react with specific target molecules in contrast with immune reaction, we undertook to answer the question whether there is any specific target gene (s) in this carcinogenesis model. By genetically analyzing F_1 hybrid rats, we found two chromosomal areas that showed a high incidence of loss of heterozygosity, which lead to a finding that p15^<INK4B>/p16^<INK4A> tumor suppressor genes are one of the major pathways responsible for this oxystress-induced cancer. Furthermore, by screening 84,000 transcripts by differential display techniques, we found that at least 15 genes associated with stress-response or cellular proliferation are differentially expressed in this model. We believe that not only genetic changes but also epigenetic changes play a role in oxidative stress-induced carcinogenesis.
日本環境変異原学会の論文
2001-12-22

酸化ストレス発がんの分子機構とその標的遺伝子 : 第12回公開シンポジウム : 活性酸素の分子病態学

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