TRACKING THE ERRANT CELL AFTER THE ATOMIC BOMBINGS: WHAT WENT WRONG?

Abstract— Epidemiological data collected after the atomic-bomb blasts of Hiroshima and Nagasaki have established a link between radiation exposure and human cancer development and are the major source of information for current radiation-induced cancer risk assessment. To determine the mechanistic basis for radiation carcinogenesis, retrospective molecular analyses of archival hepatocellular carcinoma tissues from the atomic-bomb survivors were conducted. The tumor suppressor genes p53 and M6P/IGF2r were examined. HCC cases had either p53 mutations or M6P/IGF2r mutations, but rarely both. Moreover, the frequency of cases with M6P/IGF2r mutations actually decreased with dose, while those for p53 increased. This implies two independent selection processes leading to liver cancer and that in radiation-induced HCC tumors the spectrum of molecular changes is different from that in “background” tumors.

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