Cytotoxicity of the dicarboximide fungicides, vinclozolin and iprodione, in rat hepatoma-derived Fa32 cells.
Dicarboximide fungicides are widely used to control various fungal species. Their primary action is not known, due to a lack of knowledge concerning the mechanism of action of the dicarboximide group. The cytotoxicities of vinclozolin and iprodione in rat hepatoma-derived Fa32 cells were investigated. Cytotoxicity was measured by neutral red uptake inhibition after treatment for 24 hours. Iprodione was more toxic than vinclozolin. Vinclozolin was less toxic in glutathione-depleted cells than in control cells. This was also true for iprodione at lower concentrations, but iprodione became more toxic at higher concentrations. Both the fungicides increased the endogenous glutathione content by 20% after 1 hour. After 24 hours, the glutathione content was doubled by vinclozolin, but was not affected by iprodione. No effect on glutathione S-transferase activity or reactive oxygen species formation could be observed. Cytochrome P450-dependent ethoxyresorufin-O-deethylase and pentoxyresorufin-O-depentylase activities were moderately activated by iprodione and strongly activated by vinclozolin. A glutathione-related cytochrome P450-dependent metabolic attack of vinclozolin and iprodione could be responsible for their cytotoxicity in Fa32 cells. Further research is needed to fully elucidate these (or other) mechanisms.
Dierickx
Paul J
PJ
Afdeling Toxikologie, Laboratorium Biochemische Toxikologie, Institituut voor Volksgezondheid, Wytsmanstraat 14, 1050 Brussels, Belgium. p.dierickx@iph.fgov.be
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005659:Fungicides, Industrial / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D006827:Hydantoins / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D010080:Oxazoles / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured
D005659:Fungicides, Industrial; D006827:Hydantoins; D010080:Oxazoles; D000620:Aminoimidazole Carboxamide; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D005978:Glutathione; C025643:vinclozolin; C033148:iprodione