| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
To examine the effect of environmental polluting substances on respiratory cells, we measured cytotoxicity of heavy metals, such as nickel, cdmium, mercury, lead, and manganese in primary culture of alveolar type II epithelial cells.
Cytotoxic potency of mercury was more intensive than of cadmium, however, both these metals demonstrated a dose-dependent increase of the cytotoxicity. There was no difference among the compounds of the heavy metals in the cytotoxic potency. Under the same conditions, nickel, lead, and manganese revealed no cytotoxic effect. Nickel completely inhibited a metabolic activity of mitochondria. Screening of lung toxicity by detecting the primary culture of alveolar type II epithelial cells was efficient, simple, and highly reproducible procedure.
To explain the mechanism of cell death induced by heavy metals, we studied the effect of them on damage of nuclear DNA in alveolar type II epithelial cells. The fragmentation of DNA,which is detected in apoptotic cells, was significantly induced in cells exposed by nickel. Follwed by mercury and cadmium, nickel was demonstrated as the most potent alter agent by rank order of the fragmentation of DNA.The fragmentation of DNA induced by lead and manganese remained unaffected. Amount of fragmentation of DNA in cells exposed by nickel decreased without cells' death after 6 hours of exposure. It, therefore, indicated that mechanisms that provide reparation of DNA may start just after DNA was damaged.
These results are indicating that the sensitivity of alveolar type II epithelial cells to the cytotoxicity induced by heavy metals is different. Moreover, evidence suggest that expression of mechanisms of the cytotoxicity varies and depends on heavy metal.
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