Distribution and retention of cadmium in metallothionein I and II null mice
Distribution and retention of cadmium in metallothionein I and II null mice
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DOI：
10.1006/taap.1996.0033
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发表时间：
1996-02-01
影响因子：
3.8
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
--
作者：
Liu, J;Liu, YP;Klaassen, CD
众所周知，镉(Cd)在体内具有较长的生物半衰期，可能是由于其与金属硫蛋白(MT)的结合。本研究旨在利用MT-I和MT-II基因缺失(MT-Null)小鼠来确定MT在Cd的组织分布和保留中的作用。给小鼠灌胃(CdCl2)-Cd-109(15 mU/kg，25 mU Ci/kg，ip)，分别于2小时、1、2、3、7、15天测定14个主要脏器的放射性。MT缺失型小鼠体内MT的缺乏不影响Cd的初始组织分布，因为对照组(C57BL/6J)和MT缺失型小鼠在给药后2小时的组织分布相似(分别为剂量的74%和72%)。然而，在MT缺失的小鼠中，Cd的消除速度比对照小鼠快得多。在对照组小鼠中，大约40%的镉在给药24小时后在肝脏中被发现，并且大多数与MT结合。而MT缺失组小鼠肝脏中仅有20%的Cd存在，且未与MT结合。给药1周后，MT缺失组小鼠肾脏、胰腺和脾中Cd含量也低于对照组。在15天的时间里，对照组和MT缺失型小鼠在其他器官中的Cd保留量没有明显差异。对照组小鼠肾脏中Cd浓度随时间延长而持续增加，而MT缺失组小鼠肾脏中Cd浓度无明显变化，提示肾脏中Cd的一个重要来源是对镉的摄取。综上所述，目前的数据表明，MT在Cd在组织中的初始分布中不起作用，但在Cd的消除中起主要作用，特别是在肝、肾和胰腺中。这些数据支持这样的结论，即Cd在体内的持久性至少部分是由于Cd与组织中MT的结合。(C)1996年学术出版社。
Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its binding to metallothionein (MT). This study was designed to determine the role of MT in the tissue distribution and retention of Cd using MT-I and -II null (MT-null) mice. Mice were given (CdCl2)-Cd-109 (15 mu mol/kg, 25 mu Ci/kg, ip), and radioactivity was quantified in 14 major organs at 2 hr, 1, 2, 3, 7 and 15 days thereafter. The lack of MT in MT-null mice did not affect the initial tissue distribution of Cd, as similar amounts of Cd were distributed in control (C57BL/6J) and MT-null mice 2 hr after Cd administration (74% vs 72% of the dose, respectively). However, the elimination of Cd was much faster in MT-null mice than in control mice. In control mice, approximately 40% of Cd administered was found in liver 24 hr after administration, and the majority was bound to MT. In contrast, only 20% of Cd was found in liver of MT-null mice, which was not bound to MT. Cd concentrations in kidney, pancreas, and spleen were also lower in MT-null than in control mice 1 week after administration. No apparent difference in Cd retention in other organs was noted between control and MT-null mice over the 15-day period. Cd concentration in kidney continued to increase with time in control but not in MT-null mice, indicating that an important source of Cd in the kidney is the uptake of CdMT. In conclusion, the present data indicate that MT does not play a role in the initial distribution of Cd to tissues, but does play a major role in the elimination of Cd, especially from liver, kidney, and pancreas. These data support the conclusion that the persistence of Cd in the body is at least partially due to Cd binding to MT in tissues. (C) 1996 Academic Press, Inc.