Reactive oxygen species mediate Terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins

Jui Hsiang Hung, Chia Yun Chen, Hany A. Omar, Kuo-Yuan Huang, Che Chia Tsao, Chien Chih Chiu, Yi Ling Chen, Po Han Chen, Yen Ni Teng

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Abstract

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.

Original languageEnglish
Pages (from-to)1888-1898
Number of pages11
JournalEnvironmental Toxicology
Volume31
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

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All Science Journal Classification (ASJC) codes

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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