2001 Fiscal Year Final Research Report Summary
Role of metallothionein as an inhibitory factor in metal carcinogenesis
| Project/Area Number |
12670380
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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 |
Public health/Health science
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| Research Institution | National Institute for Environmental studies |
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Principal Investigator |
SATOH Masahiko National Institute for Environmental studies, Environmental Health Sciences Division, Senior Researcher, 環境健康研究領域, 主任研究員 (20256390)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Metallothionein / Metal carcinogenesis / Arsenic / Dimethylarsenic acid / Cadmium / Gene knock-out mouse / DNA damage / 8-OHdG |
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| Research Abstract |
To elucidate the role of metallothionein (MT) in the metal carcinogenesis, we examined the effect of MT on the genotoxicity and carcinogenicity caused by dimethylarsenic acid (DMA) that is a metabolite of inorganic arsenic, and cadnrium using MT-null mice whose expression of MT-1 and MT-II, major isoforms of MT, were suppressed.
1. Effect of MT on the enotoxicit of DMA and cadmium :
DMA produced DNA strand breaks in peripheral blood cells and increased 8-0HdG Ievels in serum and urine in both MT-null mice and wild-type mice in a dose-dependent manner. However, the production of DNA strand breaks and the increase of 8-0HdG were significantly higher in the MT null mice than that of the wild-type mice. On the other hand, in the increase of urinary 8-0HdG by cadmium, MT-null mice were more susceptible than wild-type mice. These results suggest that MT plays a protective role against the genotoxicity of DMA and cadmium.
2. Effect of MT on the carcino enicit of DMA and cadmium :
We examined the induction of tumors by DMA and cadmium using MT-null mice and wild-type mice, whereas the tumor was not induced by DMA and cadmium in both types of mice. Thus, doses of DMA and cadmium were not adequate in this study. In the future study, it is necessary to examine the effect of MT on the carcinogenicity of DMA and cadmium using various conditions of dose and administration period in MT-null mice and wild-type mice.
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