Mediation of gamma-hexachlorocyclohexane-induced DNA fragmentation in HL-60 cells through intracellular Ca2+ release pathway.
Food Chem Toxicol
; 36(6): 513-20, 1998 Jun.
Article
in En
| MEDLINE
| ID: mdl-9674959
ABSTRACT
The cytotoxicity of gamma-hexachlorcyclohexane (gamma-HCC) was evaluated in HL-60 cells. Gamma-HCC dose-dependently induced cytotoxicity of HL-60 with an IC50 value of 60+/-5 microM. The gamma-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. Gamma-HCC induced DNA fragmentation of HL-60 cells in a dose-, time- and Ca2+-dependent manner. The DNA fragmentation induced was inhibited by intracellular Ca2+ chelator, calmodulin antagonist and Ca2+ sensitive endonuclease inhibitor. Gamma-HCC caused a steady increase in the cytosolic free Ca+ concentration due to release from intracellular stores. Neither the DNA fragmentation nor the increase of intracellular Ca2+ induced by gamma-HCC was inhibited by the removal of extracellular Ca2+. These data suggested that the cytotoxicity of gamma-HCC in HL-60 cells is mediated by the increase of intracellular Ca2+ concentration and the activation of Ca2+-dependent endonuclease, which triggers apoptosis in a Ca2+ and calmodulin-dependent manner.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hexachlorocyclohexane
/
Carcinogens
/
Calcium
/
HL-60 Cells
/
DNA Fragmentation
/
Insecticides
Limits:
Humans
Language:
En
Journal:
Food Chem Toxicol
Year:
1998
Document type:
Article