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.