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

为了更详细地评价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，我们从Ah应答和无应答的小鼠中分别选择了3个近交系。将TCDD和PenCDF分别以20ug/kg和60ug /kg的剂量腹腔给药6株小鼠，每2周1次（6次），末次给药3 d后处死动物，采用多项毒理学指标检测TCDD和PenCDF对小鼠的毒性作用。对实验数据进行了分析，以确定Ah基因型是否参与其毒性，得到的结果如下：1。TCDD治疗后肝脏和胸腺重量的变化与Ah反应性的相关性高于PenCDF治疗后。2. 在肝和肺的芳烃羟化酶（AHH）诱导性方面，我们没有发现AHH应答株和无应答株之间有任何差异。然而，AHH对肾的诱导率在AHH应答株中比在AHH无应答株中高得多。3. 由于TCDD或PenCDF引起的肝脏组织病理学变化似乎在嗜水气杆菌应答株中比在嗜水气杆菌无应答株中更大。在包括肾脏在内的其他器官中，我们没有观察到任何可归因于化学物质的生理病理损害。4. TCDD或PenCDF的免疫毒理学效应和化学物质对有丝分裂指数的影响与Ah基因型并不一定相关。综上所述，TCDD或PenCDF毒性的遗传调控似乎并不简单，我们认为某些生物因素，包括Ah位点以外的基因，参与了化学物质的物种和器官特异性毒性的表现。

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.