BMC Medicine · 2011 · 74 citations · 34 references
PharmacyPharmacologyToxicologyApoptosisImmunotoxicologyMechanisms Of ToxicityApoptosis In Immune CellsApoptosis PharmacologyApoptotic SignalingHerbicide ToxicologyImmunotoxicity Of PesticidesMolecular Mechanisms Of ToxicityAtrazine ExposureFas LigandFas Ligand-mediated ApoptosisHerbicide ImmunotoxicityImmunotoxic EffectsLymphocyte ApoptosisSpleen HistopathologySpleen Toxicity
BACKGROUND: Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR), is the most commonly applied broad-spectrum herbicide in the world. Unintentional overspray of ATR poses an immune function health hazard. The biomolecular mechanisms responsible for ATR-induced immunotoxicity, however, are little understood. This study presents on our investigation into the apoptosis of splenocytes in mice exposed to ATR as we explore possible immunotoxic mechanisms. METHODS: Oral doses of ATR were administered to BALB/C mice for 21 days. The histopathology, lymphocyte apoptosis and the expression of apoptosis-related proteins from the Fas/Fas ligand (FasL) apoptotic pathway were examined from spleen samples. RESULTS: Mice administered ATR exhibited a significant decrease in spleen and thymus weight. Electron microscope histology of ultrathin sections of spleen revealed degenerative micromorphology indicative of apoptosis of splenocytes. Flow cytometry revealed that the percentage of apoptotic lymphocytes increased in a dose-dependent manner after ATR treatment. Western blots identified increased expression of Fas, FasL and active caspase-3 proteins in the treatment groups. CONCLUSIONS: ATR is capable of inducing splenocytic apoptosis mediated by the Fas/FasL pathway in mice, which could be the potential mechanism underlying the immunotoxicity of ATR.
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Tyrone B. Hayes, Kelly Haston, Mable Tsui et al. · Nature · 2002 · 409 citations
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