Kershaw W C, Lehman-McKeeman L D, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Appl Pharmacol. 1990 Jun 15;104(2):267-75. doi: 10.1016/0041-008x(90)90301-a.
The purpose of this study was to quantitate hepatic metallothionein-I (MT-I) and metallothionein-II (MT-II) in adult mice pretreated with various dosages of selected inorganic and organic compounds and in nonchemically treated neonatal mice. Male CF-1 mice received Zn (0.38-6.0 mmol/kg, sc), Cd (5-80 mumol/kg, sc), dexamethasone (10-1000 mumol/kg, sc), or ethanol (60-180 mmol/kg, po). Liver cytosol was prepared 24 hr after the administration of each compound. In another experiment, liver cytosols were prepared from male and female neonates 1 to 35 days after parturition. MT-I and MT-II in liver cytosols were isolated by high-performance anion-exchange chromatography and quantitated by atomic absorption spectrometry. Hepatic MT-I and MT-II concentrations in adult controls were 5.1 +/- 1.3 and 3.7 +/- 1.0 micrograms/g liver, respectively. All compounds increased hepatic MT levels in a dose-dependent manner over a narrow range of dosages. The lowest dosages of Zn, Cd, dexamethasone, and ethanol that produced a significant increase in total MT content (MT-I plus MT-II) were 0.38, 0.005, 0.3, and 90 mmol/kg, respectively. Maximal induction of total MT following the highest dosages of Zn, Cd, ethanol, and dexamethasone was 58, 34, 24, and 13 times the control value (8.8 +/- 2.4 micrograms total MT/g liver), respectively. The relationship between dose and hepatic MT content was linear following ethanol administration and log-linear following Zn, Cd, and dexamethasone administration. The ratio of MT-I/MT-II was approximately 2.4 following all dosages of metals. Following low and high dosages of organic compounds, the ratio of MT-I/MT-II was approximately 1.0 and 1.5, respectively. Total MT concentration in livers of 1- to 14-day-old mice was approximately 40 times that observed in adult liver (5.5 +/- 1.6 micrograms total MT/g liver) and returned toward adult levels 21 days after parturition. The ratio of MT-I/MT-II was approximately 1.8 during Postpartum Days 1 through 14 and thereafter decreased to approximately 1.0. These results indicate that MT-I is more abundant than MT-II in mouse liver following chemical exposure and during neonatal development.
本研究的目的是对用各种剂量的选定无机和有机化合物预处理的成年小鼠以及未经化学处理的新生小鼠肝脏中的金属硫蛋白-I（MT-I）和金属硫蛋白-II（MT-II）进行定量。雄性CF-1小鼠接受锌（0.38 - 6.0 mmol/kg，皮下注射）、镉（5 - 80 μmol/kg，皮下注射）、地塞米松（10 - 1000 μmol/kg，皮下注射）或乙醇（60 - 180 mmol/kg，口服）。在给予每种化合物24小时后制备肝脏胞质溶胶。在另一项实验中，在分娩后1至35天从雄性和雌性新生小鼠制备肝脏胞质溶胶。肝脏胞质溶胶中的MT-I和MT-II通过高效阴离子交换色谱法分离，并用原子吸收光谱法定量。成年对照小鼠肝脏中的MT-I和MT-II浓度分别为5.1±1.3和3.7±1.0微克/克肝脏。所有化合物在较窄的剂量范围内均以剂量依赖性方式增加肝脏MT水平。使总MT含量（MT-I加MT-II）显著增加的锌、镉、地塞米松和乙醇的最低剂量分别为0.38、0.005、0.3和90 mmol/kg。锌、镉、乙醇和地塞米松最高剂量后总MT的最大诱导量分别是对照值（8.8±2.4微克总MT/克肝脏）的58、34、24和13倍。乙醇给药后剂量与肝脏MT含量之间的关系呈线性，锌、镉和地塞米松给药后呈对数线性关系。所有剂量的金属给药后MT-I/MT-II的比值约为2.4。低剂量和高剂量有机化合物给药后，MT-I/MT-II的比值分别约为1.0和1.5。1至14日龄小鼠肝脏中的总MT浓度约为成年肝脏中观察值的40倍（5.5±1.6微克总MT/克肝脏），分娩后21天恢复至成年水平。产后第1天至第14天MT-I/MT-II的比值约为1.8，此后降至约1.0。这些结果表明，在化学暴露后和新生期发育过程中，小鼠肝脏中MT-I比MT-II更丰富。
