Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-Pentachlorodibenzofuran and Susceptibility of Hosts to the Chemicals

2,3,7,8-四氯二苯并-对二恶英和2,3,4,7,8-五氯二苯并呋喃的毒性及宿主对化学品的敏感性

基本信息

批准号：
62480179
负责人：
NAGAYAMA Junya
金额：
$ 4.03万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

In order to evaluate in more detail the segregation of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) or 2,3,4,7,8-pentachloro dibenzofuran(PenCDF) with the Ah genotype, we used three inbred strains of mice chosen from each of the Ah responsive and nonresponsive ones.TCDD and PenCDF were intraperitoneally administered to the six strains of mice in doses of 20ug/kg and 60 ug/kg, respectively, once every two weeks (6 times), three days after the last treatment, the animals were killed and then we examined the toxicity caused by TCDD or PenCDF by using several toxicological indices. Experimental data were analyzed for for the involvement of the Ah genotype in their toxicity and results obtained were as follows : 1. Changes in the weight of the liver and thymus after TCDD treatment showed higher correlation with the Ah responsiveness than those after the PenCDF treatment. 2. In aryl hydrocarbon hydroxylase (AHH) inducibility of the liver and lungs, we could not find any difference between the Ah responsive and nonresponsive strains. AHH inducibility, however, of the kidneys was much higher in the Ah responsive strains than in the Ah nonresponsive ones. 3. Histopathological changes in the liver due to TCDD or PenCDF seemed to be greater in the Ah responsive strains than in the Ah nonresponsive ones. We could not observe any hystopathological lesion attributable to the chemicals in other organs, including the kidneys. 4. Immunotoxicologic effect of TCDD or PenCDF and effect of the chemicals on the mitotic index did not necessarily correlate with the Ah genotype.Based on the results described above, genetic regulations of the toxicity induced by TCDD or PenCDF seem not to be simple and we consider that some biological factors, including genes other than the Ah locus, are involved in the manifestations of the species and organ specific toxicity of the chemicals.

为了更详细地评估 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 或 2,3,4,7,8-五氯二苯并呋喃 (PenCDF) 的毒性与 Ah 基因型的分离，我们使用了从Ah反应性和非反应性小鼠中选出的三种近交系小鼠。TCDD和PenCDF按剂量腹膜内施用到六种小鼠品系中分别为20ug/kg和60ug/kg，每两周一次（6次），最后一次治疗后三天处死动物，然后通过多项毒理学指标检测TCDD或PenCDF引起的毒性。对Ah基因型参与其毒性的实验数据进行了分析，得到的结果如下： 1.TCDD治疗后肝脏和胸腺重量的变化显示出与Ah反应性的相关性高于PenCDF治疗后的相关性。 2.在肝脏和肺的芳烃羟化酶(AHH)诱导能力方面，我们没有发现Ah反应菌株和非反应菌株之间存在任何差异。然而，Ah 反应菌株中肾脏的 AHH 诱导能力比 Ah 无反应菌株高得多。 3. TCDD 或 PenCDF 引起的肝脏组织病理学变化似乎在 Ah 反应菌株中比在 Ah 无反应菌株中更大。我们无法观察到其他器官（包括肾脏）中化学物质引起的任何组织病理学病变。 4. TCDD或PenCDF的免疫毒理学作用以及化学物质对有丝分裂指数的影响并不一定与Ah基因型相关。基于上述结果，TCDD或PenCDF诱导的毒性的遗传调控似乎并不简单，我们考虑到一些生物因素，包括 Ah 基因座以外的基因，与化学品的物种和器官特异性毒性的表现有关。