Abstract
The cytotoxicity of γ-hexachlorcyclohexane ( γ-HCC) was evaluated in HL-60 cells. γ-HCC dose-dependently induced cytotoxicity of HL-60 with an IC 50 value of 60±5 μ m. The γ-HCC treated cells showed some characteristic changes of apoptosis, including blebbing of the membrane, condensation of the nuclear chromatin, vacuolation of cytoplasm and internucleosomal DNA fragmentation. γ-HCC induced DNA fragmentation of HL-60 cells in a dose-, time- and Ca 2+-dependent manner. The DNA fragmentation induced was inhibited by intracellular Ca 2+ chelator, calmodulin antagonist and Ca 2+ sensitive endonuclease inhibitor. γ-HCC caused a steady increase in the cytosolic free Ca 2+ concentration due to release from intracellular stores. Neither the DNA fragmentation nor the increase of intracellular Ca 2+ induced by γ-HCC was inhibited by the removal of extracellular Ca 2+. These data suggested that the cytotoxicity of γ-HCC in HL-60 cells is mediated by the increase of intracellular Ca 2+ concentration and the activation of Ca 2+-dependent endonuclease, which triggers apoptosis in a Ca 2+ and calmodulin-dependent manner.
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