Disruption of mitochondrial complexes, cytotoxicity, and apoptosis results from Mancozeb exposure in transformed human colon cells.

ABSTRACT

Ethylene bisdithiocarbamate pesticides, including Mancozeb (MZ), are used as fungicides. Effects of MZ on apoptosis induction and mitochondrial activity of HT-29 colon cells were investigated. MZ exposed cells exhibited blebbing and cellular membrane disruption in scanning electron micrographs. Positive fluorescent staining with Annexin V at doses of 60-140 µM supports apoptosis as the mechanism of cell death. Activity of all electron transport chain complexes were evaluated. Mitochondrial Complex I activity was decreased in 100 µM treated cells. Mitochondrial Complex III activity was decreased in 60 and 100 µM MZ treated cells. Mitochondrial Complex II and Complex IV activities were decreased in cells treated with 60, 100, and 140 µM. Cells treated with 60 µM exhibited a decrease in Complex V enzyme activity. It is concluded that MZ exposure inhibits all mitochondrial complexes of HT-29 cells and that positive fluorescent microscopy and blebbing support previous studies of cell death via apoptosis.