| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
The roles of Mn transport system on the accumulation and toxicity of Cd were studied using both in vitro and in vivo systems. Cellular accumulation of Cd in MT null cells was inhibited by simultaneous addition of Mn or Zn in the medium dose-dependently. In parallel, cytotoxicity of Cd was inhibited by Mn and Zn dose-dependently, suggesting that the transport system having high affinity for Cd, Mn and Zn plays an important role in Cd incorporation into cells. In mice, simultaneous administration of Mn or Co with Cd showed marked decreases in hepatotoxicity and testicular hemorrhage caused by Cd. These effects were also observed in metallothionein knockout mice, suggesting that metallothionein is not involved in the protection by Mn and Co. However, tissue Cd concentrations were not altered, by co-administration of Mn or Co with Cd. Although protective effects of Mn and Co on Cd toxicity were not explained by the change in tissue accumulation of Cd, a novel role of IL-6 in the protection against Cd toxicity was implicated. These data suggest that Mn is involved in the deposition and toxicity of Cd in specific cell lines but not all cells of mammals. Involvement of cytokine, especially IL-6, in in vivo effects of Mn and Co on Cd toxicity should be clarified in future studies.
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