Abstract
In vivo exposure to paraquat, a bipyridyl herbicide, is associated with selective necrosis of type I and type II alveolar pneumocytes. We examined the influence of paraquat on cell growth, DNA and protein synthesis in human and rat lung epithelial and fibroblast cell lines, to determine the effects and affinity of the chemical in vitro for cells of various origins. Cells were incubated with [3H]-thymidine or [3H]-proline in the absence or presence of 0.05–10mM paraquat for periods of 6 or 24 hours. Cell cultures grown in the presence of 50–200μM paraquat exhibited significantly lower cell numbers than comparable controls after 3 days. The suppression of DNA synthesis by paraquat was dose-dependent, but did not rely on the length of exposure. Paraquat inhibited protein synthesis and selectively decreased net production of low molecular weight proteins. NADPH levels were the same in both control and treated cultures. [14C]-Paraquat was accumulated during a 4-hour exposure period via an active non-competitive process. The results suggest that lung fibroblasts are as sensitive to the herbicide as epithelial cells. In addition, paraquat appears to interfere with transcription and/or translation by its ability to generate superoxide radicals, rather than by depletion of reducing equivalents.
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