Vickers A E, Sloop T C, Lucier G W
Environ Health Perspect. 1985 Feb;59:121-8. doi: 10.1289/ehp.59-1568090.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons are a highly toxic class of environmental contaminants, as evidenced by numerous cases of accidental poisonings of human and animal populations and their extreme toxic potency in laboratory animals. The proposed model for the mechanism of action of TCDD and related compounds is analogous to that of the steroid hormones, which modulate gene expression through a receptor mechanism. In the steroid receptor model, the compound enters the cell cytoplasm where it acts as a specific ligand, binding selectively to a high affinity receptor protein. Bound to the appropriate ligand, the receptor concentrates in the nucleus where its increased association with chromatin leads to altered gene expression. This model has been useful in characterizing the Ah receptor; however, it does not provide a unifying hypothesis for all biochemical and toxic effects associated with exposure to halogenated aromatic hydrocarbons. Several findings suggest that a primary factor in determining TCDD toxicity might be tissue and species specific factors that control the actions of Ah receptor(s) in target tissues. Furthermore, numerous mechanisms might be involved. Clarifying the mechanism(s) for TCDD toxicity would enhance our ability to predict human health consequences to toxic halogenated aromatic hydrocarbons and would provide a more rational basis for risk analysis.
2,3,7,8-四氯二苯并-对-二噁英（TCDD）及相关卤代芳烃是一类剧毒的环境污染物，人类和动物群体的众多意外中毒事件以及它们在实验动物中的极高毒性都证明了这一点。TCDD及相关化合物作用机制的 proposed 模型类似于类固醇激素的作用机制，类固醇激素通过受体机制调节基因表达。在类固醇受体模型中，化合物进入细胞质，在那里它作为一种特异性配体，选择性地与高亲和力受体蛋白结合。与适当的配体结合后，受体集中在细胞核中，其与染色质结合增加导致基因表达改变。该模型在表征芳烃受体方面很有用；然而，它并没有为与接触卤代芳烃相关的所有生化和毒性效应提供一个统一的假说。一些研究结果表明，决定TCDD毒性的一个主要因素可能是控制靶组织中芳烃受体作用的组织和物种特异性因素。此外，可能涉及多种机制。阐明TCDD毒性的机制将提高我们预测有毒卤代芳烃对人类健康影响的能力，并将为风险分析提供更合理的基础。
