Effects of Captan on DNA and DNA metabolic processes in human diploid fibroblasts.
The fungicide Captan has been examined for its effects on DNA and DNA processing in order to better understand the genotoxicity associated with this agent. Captan treatment resulted in production of DNA single strand breaks and DNA-protein cross-links and elicited an excision repair response in human diploid fibroblasts. Captan was also shown to inhibit cellular DNA synthesis and to form stable adducts in herring sperm and human cellular DNA. Misincorporation of nucleotides into Captan-treated synthetic DNA templates was significantly elevated in an in vitro assay using E. coli DNA polymerase I, suggesting that DNA adduct formation by Captan could have mutagenic consequences. In sum, these studies demonstrate that Captan is capable of interacting with DNA at a number of levels and that these interactions could provide the basis for Captan's genotoxicity. The extreme cytotoxicity of this fungicide, however, could be due to other cellular effects since at the IC50 for cell killing, approximately 0.8 microM, none of the above genotoxic events could be detected by the methods employed.
Snyder
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Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
D002215:Captan / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D003841:Deoxycytidine / Q000378:metabolism; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009153:Mutagens / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000378:metabolism*; D012867:Skin; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D009153:Mutagens; D011506:Proteins; D003841:Deoxycytidine; D014316:Tritium; D012313:RNA; D004247:DNA; D002215:Captan; D013936:Thymidine