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原爆被爆者肝癌でのp53突然変異頻度の線量依存的増加： 岩元 奎介S¹、水野 照美¹、徳岡 昭治²、馬淵 清彦²、瀬山 敏雄²（¹放影研・放生部、²放影研・疫学部）

A dose dependent increase in the frequency of p53 mutations in hepatocellular carcinomas of the atomic bomb survivors: Keisuke S IWAMOTO¹, Terumi MIZUNO¹, Shoji TOKUOKA², Kiyohiko MABUCHI² and Toshio SEYAMA¹ (¹Depts .of Radiobiol. and ²Epidemiol., Rad. Effects Res. Found.)

The mechanistic role of ionizing radiation in the dose dependent increased frequency of HCC among the atomic-bomb (A-bomb) survivors of Hiroshima and Nagasaki, following a relatively long latency period, is not known. To shed some light on the molecular events that may in part help to explain the heightened risk of A-bomb-induced HCCs, we have analyzed the p53 gene in the HCC tissues of 120 survivors exposed to various doses ranging from 0 mSv to 1569 mSv (liver dose). There was a statistically (logistic regression method) significant dose response in the percent of HCC cases harboring a p53 point mutation. The dose-dependent enrichment of cells with p53 mutations in the tumors is probably caused by expansion of cells with p53 mutations plus mutations in other genes that allow unregulated growth. The direct radiation target is more likely to be a gene that is changed into a mutator by a radiation-induced mutation. The induction of a mutator gene would be expected to increase with dose and would allow a single cell or its progeny to accumulate multiple mutations necessary for the conversion of a normal to a cancer cell.