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Exposure to mixtures of endosulfan and zineb induces apoptotic and necrotic cell death in SH‐SY5Y neuroblastoma cells, in vitro
Author(s) -
Jia Zhenquan,
Misra Hara P.
Publication year - 2007
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1218
Subject(s) - apoptosis , programmed cell death , sh sy5y , biology , neuroblastoma , neurotoxicity , in vivo , necrosis , toxicity , cytotoxicity , annexin , microbiology and biotechnology , chemistry , toxicology , in vitro , cell culture , biochemistry , genetics , organic chemistry
A number of epidemiological studies have demonstrated a strong association between the incidence of Parkinson's disease and pesticide exposure. Earlier it was demonstrated that exposure to the pesticides endosulfan and zineb, alone and in combination, caused neurodegeneration in vivo . It was hypothesized that these pesticides cause neurotoxicity, in part, by enhancing apoptotic cell death. SH‐SY5Y human neuroblastoma cells, which retain a catecholaminergic phenotype, were exposed to endosulfan, zineb or a combination of these chemicals, in vitro . For mixture studies, concentrations of pesticides (100 µ m each) were chosen based on LC 25 (lethal concentration) that would result in minimum cell death. Exposure to a mixture of pesticides exhibited significantly ( P ≤ 0.05) higher toxicity than each one alone. Both pesticides were found to cause apoptotic cell death that was concentration (50–400 µ m ) dependent. A flow cytometric (7‐aminoactinomycin D) assay was used to distinguish live, early apoptotic and late apoptotic/necrotic populations. Exposure to mixtures of the pesticides enhanced both early apoptosis and late apoptosis/necrosis compared with either chemical alone. Visual evaluation using a DNA ladder assay and a fluorescence Annexin V/PI assay confirmed the contribution of both apoptotic and necrotic processes. These findings suggest that the cytotoxicity of endosulfan and zineb, both individually and in mixtures, is associated with the occurrence of early and late apoptotic/necrotic processes in SH‐SY5Y human neuroblastoma cells and support the contention that pesticide‐induced neuronal cell death leading to neurodegenerative disease may, at least in part, be associated with early and late apoptosis of dopaminergic neurons. Copyright © 2007 John Wiley & Sons, Ltd.