Method for evaluation of immunotoxicity of dioxin compounds using human T-lymphoblastic cell line, L-MAT.
Caspase-3 was activated in apoptotic L-MAT cells by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment with tributyltin, which has been reported to induce apoptosis in rat thymocytes, also activated caspase-3 and led to cell death in L-MAT cells. Blocking caspase-3 activity with the peptide inhibitor, DEVE-CHO, prevented TCDD from inducing subsequent apoptotic changes. The potent Ah receptor ligand, 2,3,7,8-tetrachlorodibenzofuran (TCDF), the low acute toxicity compound, 1,2,3,4,6,7,9-heptachlorodibenzo-p-dioxin (HCDD), and one of the major contaminants in human milk, 3,3',4,4',5-pentachlorobiphenyl (PCBP), increased the activation level of caspase-3, each in a dose-dependent manner. Thus, we propose that measuring caspase-3 activation in the human T-lymphoblastic cell line, L-MAT, is a useful evaluation method for the immunotoxicity of dioxin compounds.
Kikuchi
H
H
Department of Molecular Genetics, Institute of Development. Aging and Cancer, Tohoku University, Sendai, Japan. hkikuchi@idac.tohoku.ac.jp
Shibazaki
M
M
Ahmed
S
S
Baba
T
T
D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004147:Dioxins / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D004147:Dioxins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases