DNA 付加体, 突然変異と発がん : 第9回公開シンポジウム : モデル DNA 損傷と変異機構

概要

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Relationships between DNA adduct levels, mutant frequency and carcinogenicity were studied using a food mutagen/carcinogen, MeIQ, to which humans are exposed on a daily basis. There was no direct correlation between adduct levels and mutant frequencies in various organs (heart, liver, colon, forestomach and bone marrow) of Big Blue mice (C57BL/6N) after administration of MeIQ for 12 weeks at a concentration of 300 ppm in diet. Further, we found no direct correlation between mutant frequency and carcinogenicity in various organs in the same animals (which are sensitive to colon carcinogenesis) after feeding of MeIQ for 92 weeks; mutant frequency was highest in the colon among the 5 organs examined, but cancer incidence was highest in the liver. In the colon, mutations occurring in the stem cells of crypts are considered to be amplified 200-300 fold, however, no such amplification is present in the liver. The kinetics of mutant cell-turnover seems to be different in different tissues. This may be an important factor for the absence of a direct correlation between mutant frequency and carcinogenicity. (This paper, chaired by Shizuyo Sutou, was presented to the 9th JEMS Annual Symposium, "Synthetic Models for DNA Damage and Mutagenesis", organized by Kazuo Negishi and Hikoya Hayatsu, sponsored by the Environmental Mutagen Society of Japan, and held at Yakult Hall, Tokyo, May, 29, 1998.)
日本環境変異原学会の論文
1999-02-28