Kanno S, Aoki Y, Suzuki J S, Takeichi N, Misawa S, Suzuki K T
National Institute for Environmental Studies, Tsukuba Japan.
J Inorg Biochem. 1994 Nov 1;56(2):117-25. doi: 10.1016/0162-0134(94)85042-9.
Long-Evans rats with a cinnamon-like coat color (LEC) is an inbred strain accumulating copper (Cu) in the liver abnormally and showing spontaneous hepatitis and hepatoma. The present study was intended to clarify how Cu accumulates in the LEC rat liver. For this purpose, the distribution profiles of Cu and zinc (Zn) and the inducibility of metallothionein (MT) synthesis were examined in the liver between Cu-loaded Long Evans agouti (LEA, the original strain of LEC) rats and were compared with those in control LEC rats. LEA rats (female, five weeks old) were injected subcutaneously with CuCl2 daily at a dose of 3 mg Cu/kg body weight for 2, 4, 6, and 9 days. The concentration of Cu (124 micrograms/g) accumulated in the LEA rat liver after four injections was comparable to that in control LEC rats. Only 20% of Cu in the liver of LEA rats was recovered in the supernatant fraction in the form of MT, while Cu in the LEC rat liver (113 micrograms/g) was recovered mostly in the supernatant fraction, and was bound to MT. Although the increased concentration of Cu in the LEA rat liver was further elevated after additional injections of Cu, the amount of MT did not increase further. The MT mRNA content in the LEA rat liver remained lower than that of LEC rats even after further injections of Cu. Therefore, the present results suggest that LEC rats can accumulate Cu at a high concentration in the liver because of their extremely high inducibility of MT.
具有类似肉桂色被毛的Long-Evans大鼠（LEC）是一种近交系，其肝脏中异常积累铜（Cu），并表现出自发性肝炎和肝癌。本研究旨在阐明铜如何在LEC大鼠肝脏中积累。为此，研究了铜负荷的Long Evans刺豚鼠（LEA，LEC的原始品系）大鼠肝脏中铜和锌（Zn）的分布情况以及金属硫蛋白（MT）合成的诱导性，并与对照LEC大鼠进行了比较。LEA大鼠（雌性，5周龄）每天皮下注射剂量为3mg铜/千克体重的CuCl2，持续2、4、6和9天。四次注射后，LEA大鼠肝脏中积累的铜浓度（124微克/克）与对照LEC大鼠相当。LEA大鼠肝脏中只有20%的铜以MT的形式在上清液部分中回收，而LEC大鼠肝脏中的铜（113微克/克）大多在上清液部分中回收，并与MT结合。尽管额外注射铜后LEA大鼠肝脏中铜浓度的增加进一步升高，但MT的量并未进一步增加。即使进一步注射铜后，LEA大鼠肝脏中的MT mRNA含量仍低于LEC大鼠。因此，目前的结果表明，LEC大鼠能够在肝脏中高浓度积累铜是因为它们对MT具有极高的诱导性。
