Oxidative stress-induced mutagenesis and carcinogenesis in DNA repair-deficient mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 25241012
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyushu University
• Principal Investigator: TSUZUKI Teruhisa 九州大学, 医学研究院, 教授 (40155429)
• Co-Investigator(Kenkyū-buntansha): 中津 可道 九州大学, 医学(系)研究科(研究院), 准教授 (00207820) ; 大野 みずき 九州大学, 医学(系)研究科(研究院), 助教 (70380524) ; 日高 真純 福岡歯科大学, 歯学部, 教授 (80238310)
• Research Collaborator: TAKANO Noriko 九州大学, 医学部, テクニカルスタッフ
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 発がん / 酸化ストレス / 突然変異 / 細胞死 / DNA損傷

Outline of Final Research Achievements

In order to identify the gene(s) commonly mutated during the process of oxidative stress-induced carcinogenesis, we performed genome-wide mutational analysis of the small intestinal tumors induced by oxidative stress in Mutyh gene deficient mice. We searched the commonly mutated gene(s) found in independent tumor tissues. Among three independent tumors, mutations resulting in amino acid substitution were detected in 105, 100, and 67 cases, respectively, with 6 genes in all 3 tumors, 9 genes in 2 of 3 tumors in common.
We also performed retrovirus-mediated gene-trap mutagenesis and isolated several clones exhibiting an increased resistance to the killing effect of DNA-damaging agents. By the analyses of the clones, we identified Mapo1 and Hmga as new genes involved in the induction of apoptosis triggered by DNA damage.

Free Research Field

分子遺伝学