The Ah Receptor Is Not Involved in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated Apoptosis in Human Leukemic T Cell Lines

It is reported that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines and decreases the Bcl-2 protein level in these cell lines, which will help in the understanding of the molecular mechanism underlying T CDD-mediated immunotoxicity.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental pollutant causing public concern. Its toxic effects include disruption of the immune, endocrine, and reproductive systems, impairment of fetal development, carcinogenicity, and lethality in rodents. Here, we report that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines. This cell death was found not to be dependent on an aryl hydrocarbon receptor and to be inhibited by the inhibitor of tyrosine kinases and caspases. Apoptosis-linked c-Jun N-terminal kinase is rapidly activated in these cells by the treatment with TCDD. A dominant-negative mutant of c-Jun N-terminal kinase prevented cell death in the treatment with TCDD. Furthermore, TCDD decreases the Bcl-2 protein level in these cell lines. These findings will help in the understanding of the molecular mechanism underlying TCDD-mediated immunotoxicity.