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Reactive oxygen species mediate T erbufos‐induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro‐apoptotic proteins
Author(s) -
Hung JuiHsiang,
Chen ChiaYun,
Omar Hany A.,
Huang KuoYuan,
Tsao CheChia,
Chiu ChienChih,
Chen YiLing,
Chen PoHan,
Teng YenNi
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22190
Subject(s) - apoptosis , reactive oxygen species , programmed cell death , microbiology and biotechnology , chemistry , tunel assay , biology , biochemistry
Terbufos ( S ‐ t ‐butylthiomethyl‐ O,O ‐diethyl phosphorodithioate) is a highly toxic organophosphate which is extensively used as an insecticide and nematicide. Chronic exposure to terbufos causes neuronal injury and predisposes to neurodegenerative diseases. Accumulating evidence has shown that the exposure to terbufos, as an occupational risk factor, may also cause reproductive disorders. However, the exact mechanisms of reproductive toxicity remain unclear. The present study aimed to investigate the toxic effect of terbufos on testicular cells and to explore the mechanism of toxicity on a cellular level. The cytotoxic effects of terbufos on mouse immortalized spermatogonia (GC‐1), spermatocytes (GC‐2), Leydig (TM3), and Sertoli (TM4) cell lines were assessed by MTT assays, caspase activation, flow cytometry, TUNEL assay, Western blot, and cell cycle analysis. The exposure to different concentrations of terbufos ranging from 50 to 800 μM for 6 h caused significant death in all the used testicular cell lines. Terbufos increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and initiated apoptosis, which was confirmed by a dose‐dependent increase in the number of TUNEL‐positive apoptotic cells. Blocking ROS production by N ‐acetyl cysteine (NAC) protected GC‐1 cells from terbufos‐induced cell death. The results demonstrated that terbufos induces ROS, apoptosis, and DNA damage in testicular cell lines and it should be considered potentially hazardous to testis. Together, this study provided potential molecular mechanisms of terbufos‐induced toxicity in testicular cells and suggests a possible protective measure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1888–1898, 2016.