摘要 : The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to induce immunotoxicity,but relatively little is known regarding its effects on B-lymphocytes,and on avian B-cells in particular.In this stu... 展开 The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to induce immunotoxicity,but relatively little is known regarding its effects on B-lymphocytes,and on avian B-cells in particular.In this study,the avian bursal pre-B-cell line DT40 was exposed to TCDD ranging from 1 to 500 nM for 1 and 6 h.At 100 nM,TCDD caused a significant increase in the number of apoptotic cells,as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay,and induced the expression of the chicken cytochrome P450 1A4 (CYP1A4) mRNA,a hallmark of TCDD exposure.TCDD induced transient upregulation of aryl hydrocarbon receptor (AhR) mRNA.At 100 nM,both caspase 3 and caspase 9 were transiently upregulated after 1 h,but returned to normal levels after 6 h of exposure.Challenge with TCDD after AhR blockade with resveratrol,a competitive AhR antagonist,prevented changes in caspases 3 and 9 and in the AhR message itself,suggesting that the effects of TCDD were mediated via the AhR.TCDD did not cause significant changes in the relative gene expression of caspase 8,Bcl-2 and Bcl-xL.We conclude that avian DT40 pre-B-cells exposed to TCDD are susceptible to apoptosis,likely through activation of executioner caspase 3. 收起