| Project/Area Number |
17390037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | National Institute for Environmental Studies |
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Principal Investigator |
AOKI Yasunobu National Insuune for Environmental Studies, Research Center for Environmental Risk, Guest Researcher, 環境リスク研究センター, 客員研究員 (20159297)
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| Co-Investigator(Kenkyū-buntansha) |
NOHMI Takehiko National Institute of Health Sciences, Division of Genetics and Mutagenesis, Section Chief, 変異遺伝部, 室長 (30150890)
GOTO Sataro Toho University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (10012650)
MATSUMOTO Michi National Institute for Environmental Studies, Research Center for Environmental Risk, Senior Researcher, 環境リスク研究センター, 主任研究員 (60132867)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2006: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Mutagen / gpt delta mouse / benzo[a]pyrene / aging |
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| Research Abstract |
To clarify whether susceptibility to mutagens is altered during ageing, we analyze the mutation induced by benzo[a]pyrene (BaP) in the lungs of aged gpt delta mice, a model animal for detecting in vivo mutagehesis. One milligram of BaP was given intratracheally into the lung of gpt delta mice of 3,11 and 24 month (mo.) old (young, middle and old age, respectively), and mutant frequency (MF) was determined 14 days after administration. In the control mice, MF was increased depending on ageing from 0.7 x 10-5 (3 mo.) to 1.1 x 10-5 (11 mo.) but was not elevated at 24 mo.. In BaP-treated mice, MF was highest at 3.mo. (2.7 x 10-5) and decreased at 11 mo. (1. 7 x 10-5), but gradually increased at 24 mo.. MF in BaP-treated mice was 3, 9-,1.4-and 2.3-fold higher than that in the control mice at 3 mo., 11 mo. and 24 mo.. These observation showed that susceptibility to BaP was highest at young age and was reduced at middle age but was elevated again at old age.
Mutation spectrum was drastically altered depending on the ageing. In the control mice, G>A transition was markedly increased at 11 mo. and 24 mo. On the other hand, in BaP treated mice, G>T transversion was a major mutation at 3 mo.. This base substitution was decreased depending on ageing but G>A transition was increased. Analysis of expression of drug metabolizing enzyme showed that the level of glutathione-S-transferase (GST) α in BaP treated mouse lungs was decreased depending aging and it became to be the same as that in the control at 24 mo.. The level of GST π was elevated depending on ageing but there was no significant between BaP treated mice and age-matched control. We did not observe the relationship between MF and the expression level of drug-metabolizing enzyme.
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