Comparative cytotoxic and stress-associated effects of three triazine herbicides in PC12 cells

BACKGROUND: Atrazine, simazine, and cyanazine are structurally related triazine herbicides, but their cellular responses have not been compared extensively under the same experimental conditions. We compared cytotoxic and stress-associated responses to the three compounds in undifferentiated PC12 neuronal-like cells. METHODS: Cells were exposed to atrazine, simazine, or cyanazine at 20 or 200 μM for 12, 24, or 48 h. Relative metabolic viability, DCFH-DA fluorescence, supernatant nitrite, apoptosis-related transcripts, and protein-associated signals were assessed. RESULTS: , and the corresponding protein-associated signals also changed after exposure, consistent with altered apoptosis-related signaling. Response magnitude and time course varied among compounds and exposure conditions. CONCLUSION: Atrazine, simazine, and cyanazine produced cytotoxic and stress-associated responses in undifferentiated PC12 cells, accompanied by changes in apoptosis-related molecular markers. The study was not designed to establish a relative potency order, and direct cell-death assays are required to determine whether these molecular changes progress to apoptosis. Studies in differentiated or primary neuronal models will be needed to assess their neuronal relevance.