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Recent trend of research on the nongenotoxic mechanisms of chemical carcinogenesis

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  • 化学発がんの非遺伝毒性的メカニズムの解明に関する最近の動向

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本総説は,筆者らが進めている「低線量放射線の健康への影響と医療への応用」に関する研究に資するために調査した,化学発がんの非遺伝毒性的メカニズムの解明に関する最近の動向の概要についてまとめたものである。即ち,非遺伝毒性的発がんにおける細胞増殖,シトクロムP450誘導,酸化的ストレス,および遺伝子発現のそれぞれの役割,並びに量的な応答性について言及した。また,後成的発がんにおけるアポトーシス,およびギャップ結合による情報伝達のそれぞれの役割についても触れた。その結果,非遺伝毒性的な発がん物質の作用の様式とメカニズムやこれによる後成的な影響などについては解明さ れつつあり,特に,これらの発がん物質がゲノムDNAに対し直接的な相互作用,突然変異,修飾などを行う発がん物質とは機能的に異なった作用をすることが明らかになった。また,これらは放射線発がんなど低線量放射線の健康への影響などについて研究する上で,重要な知見となっていることもわかった。

To elucidate the health effects by low dose radiation, we reviewed the recent trend of research on the epigenetic mechanisms of chemical carcinogenesis. The following view were obtained. It has become apparent that chemical and physical agents that induce cancer may do so through different cellular and molecular mechanisms. Investigators, recognizing the apparent differences in the ways compounds participate in the carcinogenesis process, coined the phrases "genotoxic" and "epigenetic" in describing activities of chemicals and physical agents that induced cancer. The term "nongenotoxic" has to some extent replaced "epigenetic" and thus, classification of chemical carcinogens has been frequently delegated to either the genotoxic or nongenotoxic categories. Moreover, while much work remains in the understanding of the modes and mechanisms of action of nongenotoxic carcinogens and the epigenetic effects of these agents, it is apparent that this category of chemicals are functionally different than those compounds which directly interact, mutate, and modify genomic DNA.


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