Age-dependent variation for inducibility of metallothionein genes in mouse liver by cadmium.

Age-dependent variation for inducibility of metallothionein genes in mouse liver by cadmium.
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DOI:
10.1002/dvg.1020090103
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发表时间:
1988
期刊:
Developmental genetics
影响因子:
--
通讯作者:
David J. Thomas;S. Morris;P. C. Huang
David J. Thomas;S. Morris;P. C. Huang
中科院分区:
其他
文献类型:
--
作者:
David J. Thomas;S. Morris;P. C. Huang

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镉是一种有毒金属,可诱导许多组织中金属硫蛋白基因的表达,并与金属硫蛋白(一种可溶的过渡金属结合蛋白)强烈结合。本研究观察了不同日龄C57BL/6J小鼠肝脏金属硫蛋白基因表达的时间模式和积聚程度。在成年雌性小鼠体内,镉的蓄积量依赖于镉的剂量水平,并与肝脏中镉的浓度有关。肝脏中金属硫蛋白mRNA的蓄积与镉暴露时的年龄有关。在7日龄和14日龄小鼠的肝脏中,每公斤注射2毫克镉的小鼠肝脏中金属硫蛋白的mRNA水平略有增加(2到3倍)。相比之下,28日龄和56日龄小鼠的镉处理导致肝脏中金属硫蛋白mRNA水平增加了12到19倍,最大增加发生在处理后3到4小时。由于在7日龄、28日龄和56日龄小鼠的肝脏中发现了类似的镉积累模式,因此观察到肝脏金属硫蛋白mRNA诱导的年龄差异可能不是由于镉在该器官中积累的差异。综上所述,这些数据表明,控制金属硫蛋白基因表达的组织特异性因素可能解释了镉诱导这些基因的发育差异。镉处理后金属硫蛋白mRNA积聚的个体差异可能是C57BL/6J小鼠急性致死性发育差异的一个因素。
Cadmium is a toxic metal that induces the expression of metallothionein genes in many tissues and that binds avidly to metallothionein, a soluble transition metal binding protein. The present study examined the temporal pattern and magnitude of accumulation of metallothionein mRNA in liver of C57BL/6J mice of various ages treated with cadmium. In adult female mice, accumulation was dependent on the dosage level of cadmium and related to the concentration of this metal in liver. The accumulation of metallothionein mRNA in liver depended on age at exposure to cadmium. Intraperitoneal administration of 2 mg of cadmium per kg provoked small increases (two- to threefold) in levels of metallothionein mRNA in livers of 7- and 14-day-old mice. In contrast, cadmium treatment of 28- and 56-day-old mice resulted in 12- to 19-fold increases in levels of metallothionein mRNA in liver with maximum increases occurring 3 to 4 hr after treatment. Because similar patterns for the accumulation of cadmium of liver were found in 7-, 28-, and 56-day-old mice, observed age-dependent differences in induction of metallothionein mRNA in liver were probably not due to differences in the accumulation of cadmium in this organ. Taken together, these data suggest that tissue-specific factors controlling the expression of metallothionein genes may account for developmental variation in the inducibility of these genes by cadmium. Ontogenic variation in accumulation of metallothionein mRNA after cadmium treatment may be a factor in developmental variation in the acute lethality of cadmium in C57BL/6J mice.