MECHANISM OF DIOXIN TOXICITY

TCDD(2，3，7，8-四氯二苯并-对二恶英；二恶英)最多 有毒的人造化学物质。它有广泛的毒性作用。 它们既有物种特异性，也有组织特异性。消瘦，胸腺 萎缩和迟发性死亡是较常见的疾病。 效果。它也被证明是一种有效的肿瘤促进剂， 皮肤和肝脏都有。多氯二苯并呋喃(PCDF) 行为像TCDD，可以被认为是“二恶英的等价物”。在……里面 以确定这类化合物是否也 肿瘤促进剂，如果毒性当量因子衍生 从急性和短期研究适用于慢性影响，我们 正在调查2，3，4，7，8-五CDF和 1，2，3，4，7，8-六六六-CDF促进MNNG诱发的小鼠皮肤肿瘤 HRS无毛小鼠，与用 TCDD。 最近对TCDD毒性机制的研究有 对某些生长调节受体的影响，即， 表皮生长因子，糖皮质激素。我们正在调查 TCDD暴露对转化生长因子的影响 无毛小鼠皮肤中的转化生长因子β及其受体 被证明是氯痤疮的一个很好的模型，氯痤疮是一种敏感的指标 TCDD对人体的毒性。我们还在研究转化生长因子及其 人鳞状细胞癌细胞系中具有反应性的受体 对TCDD的毒性。由于对增长因素的影响(或 受体)可能涉及第二信使，我们正在启动 TCDD对多种第二信使作用的研究 系统。

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin; dioxin) is the most toxic man-made chemical. It has a broad range of toxic effects which are both species and tissue specific. Wasting, thymic atrophy, and delayed lethality are among its more common effects. It has also been shown to be a potent tumor promoter, both in the skin and liver. Polychlorinated dibenzofurans (PCDFs) act like TCDD and may be considered as "dioxin equivalents." In order to determine whether this class of compounds are also tumor promoters, and if the toxic equivalency factors derived from acute and short term studies apply to chronic effects, we are investigating the ability of 2,3,4,7,8-PentaCDF and 1,2,3,4,7,8-hexaCDF to promote MNNG-induced skin tumors in HRS hairless mice, in comparison to the results observed with TCDD. Recent studies on the mechanism of TCDD toxicity have indicated effects on certain growth modulating receptors, i.e., epidermal growth factors, glucocorticoid. We are investigating the effects of TCDD exposure on Transforming Growth Factor beta (TGF beta) and its receptor in hairless mouse skin, which has been shown to be a good model for chloracne, a sensitive indicator of TCDD toxicity in humans. We are also studying TGF and its receptors in a human squamous carcinoma line which is responsive to TCDD toxicity. Since effects on the growth factors (or receptors) may involve second messengers, we are initiating studies on the effects of TCDD on various second messenger systems.