MECHANISM OF DIOXIN TOXICITY

二恶英的毒性机制

• 批准号: 3941494
• 负责人: L S BIRNBAUM
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3941494
• 关键词: chemical carcinogenesis; dioxins; epidermal growth factor; glucocorticoids; halobiphenyl /halotriphenyl compound; squamous cell carcinoma; toxin metabolism

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.

TCDD（2，3，7，8-四氯二苯并对二恶英;二恶英）是最常见的 有毒的人造化学物质 它具有广泛的毒性作用 其具有物种和组织特异性。 胸腺萎缩 萎缩和延迟致死是其更常见的 方面的影响. 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（PCDFs） 其作用类似于TCDD，可被视为“二恶英等价物”。“在 为了确定这类化合物是否也是 肿瘤促进剂，如果毒性当量因子 从急性和短期研究适用于慢性影响，我们 正在研究2，3，4，7，8-PentaCDF和 1，2，3，4，7，8-hexaCDF促进MNNG诱导的皮肤肿瘤 HRS无毛小鼠，与用 TCDD。 近年来对TCDD毒性机制的研究 表明对某些生长调节受体，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TGF β及其受体， 已被证明是氯痤疮的良好模型，氯痤疮是一种敏感的指标， TCDD对人体的毒性 我们也在研究TGF及其 在人鳞状细胞癌细胞系中， TCDD毒性。 由于对生长因子的影响（或 受体）可能涉及第二信使，我们正在启动 TCDD对多种第二信使的影响 系统.