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)和2，3，4，7，8-五氯二苯并呋喃(PenCDF)对Ah型小鼠的毒性分离情况，我们选择了三个近交系小鼠，分别以20ug/kg和60ug/kg的剂量分别给予TCDD和PenCDF，每隔两周(6次)，最后一次治疗后3d处死动物，用多项毒理学指标检测TCDD和PenCDF的毒性。结果表明：1.TCDD治疗后小鼠肝脏和胸腺重量的变化与Ah型反应的相关性高于PenCDF治疗后。2.在肝脏和肺的芳香烃羟基酶(AHH)诱导性方面，AH反应株和无反应株之间没有发现任何差异。然而，肾脏的AHH诱导性在Ah有反应的品系中比在Ah无反应的品系中要高得多。3.由TCDD或PenCDF引起的肝脏组织病理学改变，在Ah型敏感品系中似乎比在Ah型无反应品系中更严重。我们没有观察到任何可归因于其他器官中的化学物质的病理损害，包括肾脏。4.TCDD或PenCDF的免疫毒理学效应及其对有丝分裂指数的影响并不一定与Ah型相关。以上结果表明，TCDD或PenCDF诱导的毒性的遗传调节似乎并不简单，我们认为这些化学物质的物种和器官特异性毒性的表现涉及一些生物因素，包括ah基因以外的基因。

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.