Research Project
Grant-in-Aid for Scientific Research (B)
To characterize mutations induced by oxidative stress, we analyzed the mutants arisen in gpt delta mine (transgenic mice for detecting in vivo mutation) to which a model oxidative stress inducer, potassium bromate, was orally administrated, resulting that G-to-T transversion was induced on dG (deoxyguanosine) residue on a sequence of 5’-TGAA-5’ of gpt gene in the small intestine. We also observed that this dG was oxidized to 8-oxo-deoxyguanosine. In Msh2 (DNA mismatch repair enzyme)-deficient gpt delta mice, administration of potassium bromate induced one base deletion and one base insertion of dA (deoxyadenosine) on dA-run sequences. These point mutations are shown to be those characteristics to generation of oxidative stress.
酸化ストレスによる酸化的DNA損傷の発生は、発がんと強い関連性があるとされるが、活性酸素種が「ゲノム DNA 上のどのような位置で高頻度にDNA損傷を引き起こし、突然変異誘導して発がんに至るか?」といった課題は未解決である。臭素酸カリウムの投与によりマウス小腸に発生した腫瘍において、がん原性遺伝子(Apc)に5’-T(A)GAA-3’での点突然変異が発生していることはすでに知られているが、酸化ストレスが5’-TGAA-3’など特定の塩基配列上で8-オキソデオキシグアノシン(8-oxo-dG)を生成し、さらに、突然変異を誘発して、腫瘍発生の原因となることを示唆する知見を初めて得ることができた。
All 2019 2018 2017 2016 Other
All Journal Article (12 results) (of which Int'l Joint Research: 1 results, Peer Reviewed: 11 results, Open Access: 12 results, Acknowledgement Compliant: 1 results) Presentation (47 results) (of which Int'l Joint Research: 9 results, Invited: 19 results) Book (2 results) Remarks (1 results)
Genes & Genetic Systems
Volume: 94 Issue: 1 Pages: 13-22
10.1266/ggs.18-00015
130007625024
Food Safety
Volume: 7 Issue: 1 Pages: 2-10
10.14252/foodsafetyfscj.2018014
130007627483
Exp Cell Res
Volume: 377 Issue: 1-2 Pages: 24-35
10.1016/j.yexcr.2019.02.020
Carcinogenesis
Volume: 印刷中
Food Additives & Contaminants: Part A
Volume: 35 Issue: 9 Pages: 1689-1702
10.1080/19440049.2018.1484179
Genes and Environment
Volume: 40(25) Issue: 1
10.1186/s41021-018-0113-4
Impact
Volume: 2018 Issue: 3 Pages: 63-65
10.21820/23987073.2018.3.63
Volume: 39 Issue: 1 Pages: 16-16
10.1186/s41021-016-0064-6
Cancer Science
Volume: 108 Issue: 1 Pages: 108-115
10.1111/cas.13106
In Vivo
Volume: 30 Issue: 6 Pages: 769-776
10.21873/invivo.10993
Scientific Reports
Volume: 6 Issue: 1 Pages: 32399-32399
10.1038/srep32399
Free Radic. Biol. Med.
Volume: 99 Pages: 385-391
10.1016/j.freeradbiomed.2016.08.018
http://www.nies.go.jp/whatsnew/2017/20170224/20170224-1.html