| Project/Area Number |
11670205
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | University of Tokyo |
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Principal Investigator |
NAKATSURU Yoko University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (00237314)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Hideaki University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40214142)
ISHIKAWA Takatoshi National Institution for Academic Degrees, Faculty of University Evaluation and Research, Professor, 構, 教授 (30085633)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | AhR gene / Knockout mice / Benzo[a]pyrene / DMBA / Dibenzo[a, l]pyrene / CYP1A1 / CYP1B1 / Progression / 発がん感受性 / 芳香族炭化水素 / p450CYP1A1 / 薬物代謝酵素 / 転写誘導 |
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| Research Abstract |
The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand-activated transcription factor that is considered to mediate pleiotropic biological responses such as teratogenesis, tumor induction, epithelial hyperplasia and the induction of drug-metabolizing enzymes to environmental contaminants usually represented by dioxin. AhR also bind carcinogenic aromatic hydrocarbons (AH) which is present in environmental contaminants, such as cigarette smoke and diesel exhaust. We have reported that AhR is improtant to benzo[a]pyrene (BP) induced skin tumors using AhR gene knockout mouse carcinogenesis test. In this report, to investigate the carcinogenic role of AhR on other carcinogenic AH, we examined proliferative responses and tumor induction in AhR gene knockout mice after treatment with dibenzo[a, l]pyrene (DB[a, l]P). BrdU labeling indices of the skins from AhR+/+ mice 6 days after treatment with DB[a, l]P were significantly higher than in AhR-/- mice. Accumulation of p53 and p21 by the response of genotoxic stress was also immunohistochemically detected in both AhR+/+ and AhR-/- mice, and the incidence of p53 or p21 positive cells were significantly higher in AhR+/+ mice compared to AhR-/- mice. The genotypes of AhR (-/-) and (+/+) mice were painted with 6 μg of DB[a, l]P on the back weekly for 24 weeks. Percentage of tumor bearing mice 24 weeks after the start of experiments were AhR (-/-) ; 100%, and (+/+) 30%, respectively. Malignant squamous cell carcinomas developed in AhR+/+ mouse skin (24%), but no malignant tumor was detected in AhR-/- mice.
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