Differential regulation of the major cyclin-dependent kinases, cdk2 and cdc2, during cell cycle progression in human lymphocytes exposed to heptachlor.
Heptachlor, a chlorinated hydrocarbon insecticide, has been considered an environmental contaminant with potential adverse health effects. Exposure to heptachlor may impair immune functions including the inhibition of leukocyte chemotaxis, which causes defects in host defense mechanisms. This study addresses the effects of heptachlor on the cell cycle progression of human lymphocytes. It has been found that addition of heptachlor to cultured lymphocytic cells prevents the cells from progression into the S phase of the cell cycle, with a concomitant accumulation of cells in G1 phase. An accompanying decrease (deactivation) in cyclin-dependent kinase cdk2 and dephosphorylation (activation) of cdc2 was observed. The altered cell cycle progression may trigger the cell's apoptotic potential, as indicated by the reduced amount of Bcl-2 synthesized inside heptachlor-treated cells. The interference of cell cycle progression by heptachlor was also seen with chlordane and toxaphene, two other chlorinated hydrocarbon insecticides.
Chuang
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Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis 95616, USA. rychuang@ucdavis.edu
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Chuang
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D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000096:biosynthesis*; D042846:CDC2-CDC28 Kinases; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000096:biosynthesis*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006533:Heptachlor / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis*; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014112:Toxaphene / Q000494:pharmacology
D007306:Insecticides; D006533:Heptachlor; D014112:Toxaphene; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases