Tracking the errant cell after the atomic bombings: what went wrong?
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.
Iwamoto
Keisuke S
KS
Roy E. Coats Research Laboratories, Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Box 951714, Los Angeles, CA 90095-1714, USA. kiwamoto@radonc.ucla.edu
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects*; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D009689:Nuclear Warfare; D017354:Point Mutation; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000528:radiation effects*; D012189:Retrospective Studies; D017741:Survivors
D017527:Receptor, IGF Type 2