Uroporphyria produced in mice by 20-methylcholanthrene and 5-aminolaevulinic acid.
Uroporphyria produced in mice by 20-methylcholanthrene and 5-aminolaevulinic acid.
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20-甲基胆蒽和 5-氨基乙酰丙酸在小鼠体内产生尿卟啉症。
DOI：
10.1042/bj2530357
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Sinclair,JA
中科院分区：
文献类型：
--
作者：
Urquhart,AJ;Elder,GH;Roberts,AG;Lambrecht,RW;Sinclair,PR;Bement,WJ;Gorman,N;Sinclair,JA
铁负载的雄性C57 BL/6小鼠允许自由接触5-氨基乙酰丙酸（ALA）（2 mg/ml）的水溶液作为它们唯一的饮料，在单次腹膜内剂量的20-甲基胆蒽（MC）（125 mg/kg）的9天内发展严重的尿卟啉症。在21天时，尿卟啉原脱羧酶（EC 4.1.1.37）活性小于对照活性的10%。卟啉症不依赖于铁的预处理，并在停用ALA后持续至少21天。相同剂量的MC腹腔注射后21天内不产生卟啉症。连续给药的ALA显着加速发病的铁负载雄性C57 BL/6小鼠后，单次腹腔注射六氯苯（200毫克/公斤）;小鼠苯巴比妥和ALA不会成为卟啉。在铁负荷的雄性DBA/2小鼠中，具有ALA的MC不产生卟啉症。在哺乳动物中产生尿卟啉症至少需要两个独立的事件：诱导特定形式的细胞色素P-450和刺激肝脏中血红素生物合成中间体的形成。这些结果表明，严重的，持久性卟啉症可以在哺乳动物中产生的化合物以外的多卤代芳烃，并建议类似的机制的卤代和非卤代化合物的卟啉作用的基础。
Iron-loaded male C57BL/6 mice allowed free access to an aqueous solution of 5-aminolaevulinic acid (ALA) (2 mg/ml) as their only drink, develop severe uroporphyria within 9 days of a single intraperitoneal dose of 20-methylcholanthrene (MC) (125 mg/kg). At 21 days, uroporphyrinogen decarboxylase (EC 4.1.1.37) activities are less than 10% of control activities. The porphyria is not dependent on pretreatment with iron and persists for at least 21 days after withdrawal of ALA. The same intraperitoneal dose of MC does not produce porphyria within 21 days when given without ALA. Continuous administration of ALA markedly accelerates the onset of porphyria in iron-loaded male C57BL/6 mice after a single intraperitoneal dose of hexachlorobenzene (200 mg/kg); mice given phenobarbitone and ALA do not become porphyric. MC with ALA does not produce porphyria in iron-loaded male DBA/2 mice. At least two separate events are needed to produce uroporphyria in mammals: induction of a specific form of cytochrome P-450 and stimulation of the formation of intermediates of haem biosynthesis in the liver. These results show that severe, persistent porphyria can be produced in mammals by compounds other than polyhalogenated aromatic hydrocarbons and suggest that a similar mechanism underlies the porphyrogenic action of halogenated and non-halogenated compounds.