Ethylene bisdithiocarbamate pesticides cause cytotoxicity in transformed and normal human colon cells

The effects of the fungicides Maneb, Mancozeb, and Zineb were investigated in transformed colon cells, HT-29, Caco2 and non-transformed cells, CCD-18Co. Significant decreases in viability were observed with Maneb and Mancozeb in HT-29 and CCD-18Co (80–260 μM), and Caco2 cells (40–180 μM). No significant decreases in viability were observed in all cell types up to 800 μM with Zineb. MnCl2 and ZnCl2 exposure produced no loss of viability in all cell types up to 400 μM. Light microscopy confirmed viability analysis. Lipid peroxidation was observed with Maneb and Mancozeb in cell types tested (60–200 μM). Caspase 3/7, 8, and 9 activities were observed with Maneb and Mancozeb in cell types tested (40–200 μM). Maneb and Mancozeb treated HT-29 and Caco2 cells demonstrated increases in manganese and zinc concentrations (20–200 μM). The lack of toxicity observed with Zineb, MnCl2, and ZnCl2 suggests that both the metal moiety and the organic portion of these fungicides together contribute to toxicity.

► Maneb and Mancozeb cause cytotoxicity in all cell types tested.
► A lack of toxicity was observed in colon cells treated with Zineb, MnCl2 and ZnCl2.
► Both the metal moiety and organic portion contribute to toxicity of EBDC fungicides.
► The mechanism of toxicity may be related to increases in oxidative stress.
► Maneb and Mancozeb initiate apoptosis through the intrinsic and extrinsic pathways.