| Project/Area Number |
06280102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Hokkaido University |
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Principal Investigator |
KAMATAKI Tetsuya Laboratory of drug metabolism Hokkaido University Professor, 大学院・薬学研究科, 教授 (00009177)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yoshiki Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (80292019)
NAKAYAMA Kazuo Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (20261323)
ARIYOSHI Noritaka Hokkaido University, Associate Professor, 大学院・薬学研究科, 助教授 (00243957)
FUJITA Ken-ichi Hokkaido University, Assistant Professor, 大学院・薬学研究科, 助手 (60281820)
江角 浩安 国立がんセンター, 研究所支所, 支所長 (70160364)
島田 力 大阪府立公衆衛生研究所, 薬事指導部, 主任研究員 (50158961)
船江 良彦 (舩江 良彦) 大阪市立大学, 医学部, 教授 (00047268)
杉山 雄一 東京大学, 薬学部, 教授 (80090471)
川尻 要 埼玉がんセンター, 生化学部, 主幹 (50142112)
原田 信広 藤田保健衛生大学, 医学部, 助教授 (00189705)
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| Project Period (FY) |
1999
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥160,000,000 (Direct Cost: ¥160,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1998: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1997: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1996: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 1995: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1994: ¥20,000,000 (Direct Cost: ¥20,000,000)
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| Keywords | P450 / Salmonella typhimurium / Mutation assay / Metabolic activation / Genetic polymorphism / Lung cancer / がん原物質 / トランスジェニックマウス / DNAアダクト / 発現制御 / 発現系 / チトクロームP450 / CYP1A1 / CYP1A2 / アロマターゼ / Ahレセプター / 遺伝子導入マウス / がん原物質活性化 / CYP3A4 / P450アロマターゼ |
|---|
| Research Abstract |
l. Ten strains of Salmonella typhimurium YG7108 expressing each form of human cytochrome P450 (CYP), CYP1A1, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, together with human NADPH-cytochrome P450 reductase (OR) have been established.
2. Mutagens were formed from promutagens such as aflatoxin B_1 and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone bv human CYP forms expressed in the established Salmonella cells.
3. 2-Phenylbenzotriazole derivatives, newly isolated from river water, are promutagens, were found to be activated by human CYP1A1 specifically.
4. Individuals carrying a whole deletion genotype of the CYP2A6 gene showed significantly less lung cancer risk.
5. Furthermore, it was found that the whole deletion of the CYP2A6 gene resulted in the low risk of small cell lung cancer and squamous cell lung cancer, which have been known to be caused associated with tobacco smoke.
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