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铁过载的C57BL/10小鼠体内六氯苯的命运

Fate of hexachlorobenzene in C57BL/10 mice with iron overload.

作者信息

Khanna R N, Smith A G

出版信息

Biochem Pharmacol. 1985 Dec 1;34(23):4157-62. doi: 10.1016/0006-2952(85)90209-6.

DOI:10.1016/0006-2952(85)90209-6
PMID:4062983
Abstract

The distribution of radioactivity in male C57BL/10 mice dosed with [14C]hexachlorobenzene (HCB) was followed over 21 days and found to be high in adipose tissue and adrenals, moderate in thymus whereas liver was relatively poorly labelled. A predose of iron (500 mg/kg), which greatly promotes the porphyrogenic action of HCB in this strain, had only a small effect on the distribution of radioactivity in tissues and excreta. Iron induced excretion of urinary metabolites from HCB by C57BL/10 mice but not by the insensitive DBA/2 strain. However, there was no such difference in faecal metabolites, total metabolism was only slightly increased and there was no correlation between liver porphyrin levels and urinary excretion of metabolites by individual mice. At the end of 4 weeks exposure of iron-treated C57BL/10 mice to HCB urinary metabolites fell while porphyrin excretion continued to rise. Thus the considerable sensitisation of the C57BL/10 strain after iron overload to the induction of porphyria by HCB cannot be ascribed simply to enhancement of total metabolism but must be caused either by the formation of a specific undetected metabolite or induction of some other toxic process.

摘要

对给予[¹⁴C]六氯苯(HCB)的雄性C57BL/10小鼠体内放射性分布进行了21天的跟踪,发现脂肪组织和肾上腺中的放射性较高,胸腺中的放射性中等,而肝脏中的放射性标记相对较少。预先给予铁(500mg/kg),这在该品系中极大地促进了HCB的致卟啉作用,但对组织和排泄物中放射性的分布影响很小。铁可诱导C57BL/10小鼠排泄HCB的尿液代谢物,但对不敏感的DBA/2品系则无此作用。然而,粪便代谢物没有这种差异,总代谢仅略有增加,并且个别小鼠的肝脏卟啉水平与尿液代谢物排泄之间没有相关性。在铁处理的C57BL/10小鼠接触HCB 4周结束时,尿液代谢物减少,而卟啉排泄继续增加。因此,铁过载后C57BL/10品系对HCB诱导的卟啉症的显著敏感性不能简单地归因于总代谢的增强,而必定是由某种未检测到的特定代谢物的形成或其他某种毒性过程的诱导所引起。

相似文献

1
Fate of hexachlorobenzene in C57BL/10 mice with iron overload.铁过载的C57BL/10小鼠体内六氯苯的命运
Biochem Pharmacol. 1985 Dec 1;34(23):4157-62. doi: 10.1016/0006-2952(85)90209-6.
2
Distribution, excretion and in-vivo metabolism of 14C-hexachlorobenzene and the influence of iron overload in C57BL/10 mice.
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Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism.铁-六氯苯协同作用对C57BL/10小鼠肝脏尿卟啉原脱羧酶抑制作用的机制研究
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Investigations on the role of free radical processes in hexachlorobenzene-induced porphyria in mice.自由基过程在小鼠六氯苯诱导的卟啉症中的作用研究。
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Biotransformation and porphyringogenic action of hexachlorobenzene and its metabolites in a primary liver cell culture.六氯苯及其代谢产物在原代肝细胞培养中的生物转化和致卟啉作用。
Toxicology. 1981;19(3):185-96. doi: 10.1016/0300-483x(81)90128-1.
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Genetic, iron status and sex factors of porphyria induced by hexachlorobenzene.六氯苯诱发的卟啉症的遗传、铁状态及性别因素。
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The involvement of iron and lipid peroxidation in the pathogenesis of HCB induced porphyria.铁和脂质过氧化在六氯苯诱导的卟啉病发病机制中的作用。
Biochem Pharmacol. 1985 Jan 15;34(2):161-6. doi: 10.1016/0006-2952(85)90118-2.

引用本文的文献

1
Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism.铁-六氯苯协同作用对C57BL/10小鼠肝脏尿卟啉原脱羧酶抑制作用的机制研究
Biochem J. 1986 Sep 15;238(3):871-8. doi: 10.1042/bj2380871.
2
Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload.铁过载的近交系小鼠中化学诱导形成肝尿卟啉原脱羧酶抑制剂
Biochem J. 1987 Aug 15;246(1):221-6. doi: 10.1042/bj2460221.
3
Goitre and wasting induced in hamsters by hexachlorobenzene.
六氯苯诱发仓鼠甲状腺肿和消瘦。
Arch Toxicol. 1987 Jul;60(5):343-9. doi: 10.1007/BF00295753.