Mathematical modeling in carcinogenesis to elucidate the mechanism of radiation-induced cancer

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11680555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 環境影響評価(含放射線生物学)
• Research Institution: Oita University of Nursing and Health Sciences
• Principal Investigator: KAI Michiaki OITA UNIV. NURSING & HEALTH, Professor, 看護学部, 教授 (10185697)
• Co-Investigator(Kenkyū-buntansha): MATSUURA Masaaki HIROSHIMA UNIV. RIRBM, Assoc. Professor, 原爆放射能医学研究所, 助教授 (40173794) ; OHTAKI Megu HIROSHIMA UNIV. RIRBM, Professor, 原爆放射能医学研究所, 教授 (20110463) ; NIWA Ohtsura KYOTO UNIV. RAD. BIOLOGY CENTER, Professor, 放射線生物研究センター, 教授 (80093293) ; YAMAGUCHI Naoto NATIONAL CANCER CENTER, Cancer Information Science, Head, がん情報研究部, 部長 (80119031) ; MIZUNO Shoichi TOKYOMETROPOLITAN INSTIT. GERONTOLOGY Department of Information Science, Head, 情報科学部門, 室長 (00126905) ; PIERCE Donald RADIATION EFFECT RESEARCH FUNDATION, Department of Statistics, Senior Scientis ; PRESTON Dale RADIATION EFFECT RESEARCH FUNDATION, Department of Statistics, Chief
• Project Period (FY): 1999 – 2000
• Keywords: Multistage model / atomic bomb survivors / genomic instability / DNA damage / low dose and dose-rate

Research Abstract

In the previous paradigm for mechanism of radiation-related cancer, mutational events due to direct damage to DMA could cause initiation leading to cancer. Multistage modeling can contribute to an understanding of the induction of cancer. In recent studies on multistage modeling, the epidemiological data of atomic bomb survivors are very useful for analyzing radiation carcinogenesis.
Recent biological data indicate that not direct mutation induced by radiation but indirect mutation would be relevant to radiation carcinogenesis. The phenomena of genomic instability may change our understanding of low dose and dose-rate response. In addition, it may be of much interest to verify an implication from radiation biology whether genomic instability contributes to carcinogenesis or not. A genomic instability hypothesis can provide a schematic diagram of radiation carcinogenesis.
Based on this hypothesis, carcinogenesis models considering genomic instability will be developed and analyzed using the atomic bomb survivor data in Hiroshima and Nagasaki. The hypothesis whether genomic instability is relevant to radiation carcinogenesis is not rejected if we look at the atomic bomb survivor data until 1987. Further follow-up of the cohort will be essential to validation of the models.