Ideo G, Bellati G, Bellobuono A, Mocarelli P, Marocchi A, Brambilla P
Clin Chim Acta. 1982 Apr 23;120(3):273-83. doi: 10.1016/0009-8981(82)90368-0.
Extremely small doses of TCDD have been shown to induce hepatic microsomal enzymes in animals. Whether levels of environmental exposure to TCDD were sufficient to produce enzyme induction in man, has been investigated in Seveso, where in July 1976 explosion in a factory spread toxic substances, one of which was TCDD, to the surrounding area. The hepatic microsomal enzyme activity was assessed by estimating urinary d-glucaric acid (UGA) excretion in children 6-8 years old. In 31 children, urine samples were collected between August and December 1976; in 67 other children in February 1979. As a control group 60 children living in Busto Arsizio (a small industrial town near Milan) and 26 living Cannero (a non-industrialized village on Lake Maggiore) were chosen. In the first period of collection, children with chloracne (which is considered to be a characteristic manifestation of intoxication with chlorinated products), showed significantly increased levels of UGA compared with children without chloracne. In 1979, children living in the Seveso area showed a statistically significant enhancement of d-glucaric acid excretion compared to the control groups. In conclusion, this study demonstrates that many children living in the Seveso area have an increased activity of hepatic microsomal enzymes, since, although the urinary excretion of d-glucaric acid is only an indirect measure of enzyme activity, studies in man have indicated that it is both sensitive and quantitative. As far as the cause of this increase is concerned, since it is possible to exclude the influence of alcohol, contraceptives, phenobarbitone or other drugs, it is reasonable to conclude that TCDD, a potent inducer agent, could be responsible for this phenomenon.
已证明极小剂量的2,3,7,8-四氯二苯并对二噁英（TCDD）可在动物体内诱导肝微粒体酶。在意大利塞韦索市对环境中TCDD暴露水平是否足以在人体中产生酶诱导作用进行了研究，1976年7月该市一家工厂发生爆炸，有毒物质扩散到周边地区，其中一种就是TCDD。通过估算6至8岁儿童尿中d-葡糖醛酸（UGA）排泄量来评估肝微粒体酶活性。1976年8月至12月收集了31名儿童的尿样；1979年2月收集了另外67名儿童的尿样。选取了60名居住在布斯托阿西齐奥（米兰附近的一个小工业城镇）的儿童和26名居住在卡内罗（马焦雷湖的一个非工业化村庄）的儿童作为对照组。在首次收集阶段，患有氯痤疮（被认为是氯化产品中毒的特征性表现）的儿童与未患氯痤疮的儿童相比，UGA水平显著升高。1979年，与对照组相比，居住在塞韦索地区的儿童d-葡糖醛酸排泄量有统计学意义的增加。总之，这项研究表明，许多居住在塞韦索地区的儿童肝微粒体酶活性增强，因为尽管尿中d-葡糖醛酸排泄只是酶活性的间接测量方法，但人体研究表明它既敏感又定量。就这种增加的原因而言，由于可以排除酒精、避孕药、苯巴比妥或其他药物的影响，合理的结论是，强效诱导剂TCDD可能是造成这一现象的原因。
