Tissue distribution, excretion, and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the Golden Syrian hamster.
Tissue distribution, excretion, and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the Golden Syrian hamster.
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2,3,7,8-四氯二苯并-对二恶英 (TCDD) 在金色叙利亚仓鼠中的组织分布、排泄和代谢。
DOI：
10.1016/0041-008x(80)90132-5
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发表时间：
1980
影响因子：
3.8
通讯作者：
Neal,RA
中科院分区：
文献类型：
--
作者：
Olson,JR;Gasiewicz,TA;Neal,RA
据报道，仓鼠是对2，3，7，8-四氯二苯并对二恶英(TCDD)急性毒性最不敏感的哺乳动物物种。在雄性仓鼠身上评估了单剂量[~3H]-或[~(14)C]TCDD(650μg/kg，ip或po)治疗后长达35天的命运。肝脏、脂肪组织和肾上腺的放射性含量(百分比剂量/克组织)最高。肝脏和脂肪组织的放射性被鉴定为未代谢的TCDD。尿液和粪便中的~3H或~(14)C排泄率提示为一级过程。[~3H]-TCDD和[14C]TCDD的消除半衰期(T12)分别为12.0±2.0天和10.8±2.4天(平均值±SD)。用[~3H]-TCDD和[14C]TCDD，分别从尿液和粪便中消除了约35%和50%的放射性。[~3H]TCDD灌胃给药的T12为15.0±2.5d。对接受[14C]TCDD的动物的尿液和胆汁进行高压液相色谱分析，发现了一个主要的和几个次要的放射性峰，没有一个与[14C]TCDD相对应。肝脏或脂肪组织的提取物中明显没有TCDD代谢物，这表明TCDD的生物转化产物很容易在尿液和胆汁中排泄。相对于其他物种，仓鼠体内TCDD的代谢和排泄速度的提高可能是其对TCDD毒性的异常抵抗力的部分原因，但不能完全解释。
The hamster has been reported to be the least sensitive mammalian species to the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The fate of a single dose of [3H]- or [14C]TCDD (650 μg/kg, ip or po) was assessed in male hamsters for up to 35 days following treatment. The greatest content (percentage dose/g tissue) of radioactivity was found in the liver, adipose tissue, and adrenals. The radioactivity in liver and adipose tissue was identified as unmetabolized TCDD. The rate of3H or14C elimination in urine and feces suggested a first-order process. Similar half-life of elimination (t1 2) values of 12.0 ± 2.0 and 10.8 ± 2.4 days (mean ± SD) were obtianed with ip administered [3H]- and [14C]TCDD, respectively. With both [3H]- and [14C]TCDD, approximately 35 and 50% of the radioactivity was eliminated in urine and feces, respectively. The t1 2for po administered [3H]TCDD was 15.0 ± 2.5 days. High-pressure liquid chromatography of the urine and bile of animals receiving [14C]TCDD revealed one major and several minor radioactive peaks, none of which corresponded to [14C]TCDD. The apparent absence of TCDD metabolites in extracts of liver or adipose tissue indicates that the biotransformed products of TCDD are readily excreted in urine and bile. The enhanced rate of metabolism and excretion of TCDD in hamsters relative to other species may in part contribute to, but not totally explain its unusual resistance to TCDD toxicity.