TISSUE DISTRIBUTION, METABOLISM, AND EXCRETION OF C-14 TCDD IN A TCDD-SUSCEPTIBLE AND A TCDD-RESISTANT RAT STRAIN
TISSUE DISTRIBUTION, METABOLISM, AND EXCRETION OF C-14 TCDD IN A TCDD-SUSCEPTIBLE AND A TCDD-RESISTANT RAT STRAIN
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DOI：
10.1111/j.1600-0773.1990.tb00712.x
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发表时间：
1990-02-01
期刊：
影响因子：
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通讯作者：
TUOMISTO, J
中科院分区：
文献类型：
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作者：
POHJANVIRTA, R;VARTIAINEN, T;TUOMISTO, J
在最具TCDD抗性的[Han/Wistar（H/W），LD 50> 3000 μ g/kg]和最具TCDD敏感性的[Long-Evans（L-E），LD 50约10 μ g/kg]大鼠品系中进行比较研究，以评估动力学因素在TCDD毒性中的重要性。对两种品系的年轻成年雄性动物腹膜内给予5 μ g/kg（1.9 μ Ci/kg）14 C-TCDD。在暴露后4小时、1、4、8、16和32天，每个品系处死4只大鼠。共采集22个组织沿着血液和血清进行液体闪烁计数。还分析了一半动物的每日尿液和粪便。此外，每种品系3只大鼠给予50 μ g/Kg（19 μ Ci/kg）14 C-TCDD，并在1、4或8天后准备进行全身放射自显影。用高压液相色谱法分析了四氯二苯并对二恶英代谢物，在4小时、4天或16天处死每种品系两只大鼠的肝脏，并在暴露后第1 - 4、5 - 8、13 - 16和29 - 32天收集两种品系两只大鼠的排泄物。标记物主要以TCDD代谢产物的形式经粪便排泄，消除半衰期为20.8（L-E）或21.9（H/W）天。在两种菌株中观察到非常相似的总体分布模式，与剂量无关，肝脏是主要蓄积部位。几乎所有的肝脏14C-活性被发现作为母体化合物。在甲状腺、胸腺、前列腺、肾上腺以及棕色和白色脂肪中观察到中度品系相关差异，其中在H/W大鼠中记录的值较低。在大脑中检测到位点依赖性变异。结果不支持TCDD代谢或处置对TCDD致死率的菌株差异有重大影响的观点。
A comparative study was carried out in the most TCDD-resistant [Han/Wistar (H/W), LD50 > 3000 .mu.g/kg] and the most TCDD-susceptible [Long-Evans (L-E), LD50 about 10 .mu.g/kg] rat strain to assess the significance of kinetic fators in TCDD toxicity. Young adult males of both strains were administered 5 .mu.g/kg (1.9 .mu.Ci/kg) 14C-TCDD intraperitoneally. Four rats per strain were killed at 4 hr, 1, 4, 8, 16 and 32 days after exposure. A total of 22 tissues along with blood and serum were sampled for liquid scintillation counting. From half of the animals, daily urine and faeces were also analyzed. In addition, 3 rats per strain were given 50 .mu.g/Kg (19 .mu.Ci/kg) 14C-TCDD and prepared for whole-body autoradiography after 1, 4 or 8 days. The livers of two rats per strain killed at 4 hr, 4 or 16 days, and the excreta from two rats of both strains collected on days 1-4, 5-8, 13-16, and 29-32 after exposure were analyzed for metabolites of TCDD by high pressure liquid chromatography. The label was mainly excreted in faeces as metabolites of TCDD, and the half-life of elimination was 20.8 (L-E) or 21.9 (H/W) days. A very similar overall distribution pattern was observed in both strains irrespective of dose, and the liver was the major site of accumulation. Practically all liver 14C-activity was found as the parent compound. Moderate strain-related differences were observed in the thyroid, thymus, prostate, adrenals, and brown and white fat, where lower values were recorded in H/W rats. Site-dependent variation was detected in the brain. The results do not support the view that TCDD metabolism or disposition would have a major impact on the strain difference in TCDD lethality.