Olnes M J, Verma M, Kurl R N
Department of Medicine, Brown University School of Medicine, Providence, R.I.
Exp Clin Immunogenet. 1994;11(2-3):102-9. doi: 10.1159/000424200.
To examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic gene expression in vitro, freshly isolated rat thymocytes were incubated with 10 nM TCDD, and reverse transcriptase polymerase chain reaction experiments were performed using primers specific for prostaglandin G/H synthase (PGHS) and glyceraldehyde 3-phosphate dehydrogenase. TCDD selectively repressed PGHS gene expression, with maximal inhibition occurring within 60 min. Gel retardation assays demonstrated that dioxin transiently induced binding of the ubiquitous transcription factor NF kappa B to its cognate response element at early time points. However, TCDD had little ability to induce transformation of the Ah receptor to the xenobiotic responsive element in thymic cytosol. These results indicate that TCDD exerts changes in thymocyte gene expression prior to inducing toxicity.
为了在体外研究2,3,7,8-四氯二苯并对二恶英（TCDD）对胸腺基因表达的影响，将新鲜分离的大鼠胸腺细胞与10 nM TCDD一起孵育，并使用针对前列腺素G/H合酶（PGHS）和甘油醛-3-磷酸脱氢酶的特异性引物进行逆转录聚合酶链反应实验。TCDD选择性地抑制PGHS基因表达，最大抑制作用在60分钟内出现。凝胶阻滞分析表明，二恶英在早期时间点短暂诱导普遍存在的转录因子NF-κB与其同源反应元件的结合。然而，TCDD诱导Ah受体转化为胸腺细胞质中异源生物反应元件的能力较弱。这些结果表明，TCDD在诱导毒性之前就会引起胸腺细胞基因表达的变化。
