Physiological significance of metallothionein on environmental carcinogenesis
| Project/Area Number |
12470090
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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 |
Hygiene
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| Research Institution | National Institute for Environmental Studies |
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Principal Investigator |
TOHYAMA Chiharu National Institute for Environmental Studies, Environmental Health Sciences Division, Director, 環境健康研究領域, 領域長 (10150872)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Masahiko Gifu Pharmaceutical University, Department of Hygienics, Associate Professor, 助教授 (20256390)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Metallothionein / Environmental carcinogenesis / Anticarcinogenic effect / 7, 12-dimethylbenz[a] anthracene / Benzo[a]pyren / N-ethyl-N-nitrosourea / X-irradiation / Genotoxicity / 化学発がん / 遺伝子欠損マウス / ジメチルベンズ(a)アントラセン / ベンゾ(a)ピレン / 小核試験 / 肺腫瘍 / ras遺伝子 / 皮膚腫瘍 / 胃腫瘍 |
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| Research Abstract |
To elucidate the role of metallothionein (MT) in the environmental carcinogenesis, we examined the effect of MT on the two-stage skin carcinogenesis induced by 7, 12-dimethylbenz[a]anthracene (DMBA)/12-Οtetradecanoylphorbol-13-acetate (TPA), multiple organs carcinogenesis induced by DMBA oral administration and lung carcinogenesis induced by N-ethyl-N-nitrosourea (ENU) using MT-null mice whose expression of MT-I and MT-II, major isoforms of MT, were suppressed. In addition, we also eximined the susceptibility of MT-null mice in the genotoxicity caused by DMBA/TPA, benzo[a]pyren (B[a]P) or X-irradiation.
MT-null mice were found to be much more sensitive than wild-type mice to incidence of skin tumor by DMBA/TPA combination, incidence of tumors in the stomach, liver and lung by DMBA oral administration and incidence of lung tumor by ENU treatment.Moreover, we detected transversion of A^<182> to T in codon 61 of c-Ha-ras in papilloma tissues of MT-null mice and wild-type mice treated with DMBA/TPA combination. It was showed using MT-null mice and wild-type mice that MT prevented B[a]P-induced micronucleus and X-irradiation-induced oxidative DNA damage and micronucleus. In addition, it was clear that MT has antitumorigenic potential in both the initiation and promotion stage of DMBA/TPA-induced two-stage skin carcinogenesis.
These results suggest that MT plays an important role as anticarcinogenic factor in environmental carcinogenesis.
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Report
(4 results)
Research Products
(2 results)
