An Additional Mechanism for the Cytotoxicity of 2-Chloroethylethyl Sulfide in Spleen Lymphocytes; Lysosomal Labilization

  • Choi, Dae-Sung (Advanced Technology Research Center (#6-7), Agency for Defense Development) ;
  • Shin, Sung-Ho (Advanced Technology Research Center (#6-7), Agency for Defense Development) ;
  • Kim, Yun-Bae (Advanced Technology Research Center (#6-7), Agency for Defense Development) ;
  • Cha, Seung-Hee (Advanced Technology Research Center (#6-7), Agency for Defense Development) ;
  • Sok, Dai-Eun (Advanced Technology Research Center (#6-7), Agency for Defense Development)
  • Received : 0
  • Accepted : 0
  • Published : 0

Abstract

Exposure of spleen lymphocytes to 2-chloroethylethyl sulfide (CEES) leads to a reduction of the intracellular ATP level, followed by a decrease in cell viability. Addition of nicotinamide, an inhibitor of poly(ADP-ribose) polymerase (PADPRP), restores both ATP level and viability, indicating that an activation of PADPRP is responsible for the cytotoxicity of CEES. The involvement of a $Ca^{2+}$-mediated process in cytotoxicity is suggested. Verapamil, EGTA, trifluoperazine, and butacaine exhibit a partial protection (20 to 58%) against the cytotoxicity of CEES. Investigation of the causative role of proteolytic degradation in cell death indicate that pepstatin and leupeptin exert a substantial protective effect (60 to 70%), suggesting the involvement of lysosomal destabilization in CEES-induced cytotoxicity. Also, lysosomotropic agents markedly decrease the cytotoxicity. Lysosomal labilization may be a mechanism for the cytotoxicity of CEES.

Keywords

2-Chloroethylethyl sulfide (CEES);cytotoxicity;lysosome