Molecular biological studies on environmental chemical pollutants interfering with endocrine systems

环境化学污染物干扰内分泌系统的分子生物学研究

基本信息

批准号：
10670350
负责人：
NISHIO Hisahide
金额：
$ 1.66万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We studied an endocrine disruptor, cadmium, by molecular biological methods. Our project included two studies : gene expression induced by cadmium exposure and genetic analyses of Itai-itai disease which is caused by chronic exposure to cadmium.[Gene expression induced by cadmium exposure] To clarify the effects of cadmium on the endocrine system, we firstly screen the genes responsive to cadmium in COS-7 cells with a subtractive suppressive hybridization (SSH) method. We have detected more than 100 mRNA species which were induced by cadmium exposure, and identified their origins by sequencing analysis. The genes responsive to cadmium were as follows : metallothionein II, zeta-crystalline, cytochrome C oxidase subunit IV, glutathione synthetase, serine/threonine protein kinase, heat shock protein 10, transduction beta-I subunit, tunp, lipocortin II hsp 10, hsp 40, hsp 60, hsp 86, BAG-3, complement cytolysis inhibitor (CLI) and so on. Each of them showed its characteristic expression pattern when cadmium concentration and exposure time changed. Further analyses are required to clarify the relationships between the genes responsive to cadmium and the endocrine system.[Genetic analyses of itai-itai disease] In order to clarify the role of estrogen receptor α on the pathogenesis of itai-itai disease, we examined the genotypic polymorphisms in estrogen receptor α gene of the patients with itai-itai disease and compared them with those of control subjects. We examined PuvII, XbaI RFLP polymorphism in intron 1 and AT repeat polymorphism in upstream region of the estrogen receptor α gene. The genotypic distributions of the patient group were similar to those of the control groups, hence no itai-itai disease-related pattern of genotypic distribution was observed. We conclude that polymorphisms of the gene may not be associated with itai-itai disease.

我们通过分子生物学方法研究了内分泌干扰物镉。我们的项目包括两项研究：镉暴露诱导的基因表达和慢性暴露于镉引起的痛痛病的遗传分析。[镉暴露诱导的基因表达]为了阐明镉对内分泌系统的影响，我们首先采用消减抑制杂交（SSH）方法筛选COS-7细胞中对镉敏感的基因。已检测到100多种由镉暴露诱导的mRNA种类，并通过测序分析确定了它们的起源，这些基因对镉有反应：金属硫蛋白II、zeta-结晶、细胞色素C氧化酶亚基IV、谷胱甘肽合成酶、丝氨酸/苏氨酸。蛋白激酶、热休克蛋白 10、转导 β-I 亚基、肿瘤、脂皮质素 II hsp 10、hsp 40、hsp 60、hsp 86、BAG-3、补体细胞溶解抑制剂（CLI）等在镉浓度和暴露时间变化时表现出其特征性的表达模式，需要进一步分析以阐明响应基因之间的关系。 [痛痛病的基因分析]为了阐明雌激素受体α在痛痛病发病机制中的作用，我们对痛痛病的基因型进行了研究。我们检测了痛痛病患者雌激素受体α基因的多态性，并将其与对照受试者的雌激素受体α基因内含子1的PuvII、XbaI RFLP多态性和上游区域的AT重复多态性进行了比较。患者组的基因组与对照组相似，因此没有观察到与痛痛病相关的基因型分布模式，我们得出结论，可能没有发现该基因的多态性。与痛痛病有关。