Yoshida M, Satoh M, Shimada A, Yasutake A, Sumi Y, Tohyama C
Department of Chemistry, St. Marianna University School of Medicine, Kawasaki, Japan.
Life Sci. 1999;64(20):1861-7. doi: 10.1016/s0024-3205(99)00129-0.
This study examined the protective role of metallothionein (MT) against pulmonary damage caused by acute exposure to metallic mercury (Hg0) vapor using MT-null and wild-type mice. Both strains of mice were exposed to Hg0 at 6.6 to 7.5 mg/m3 for 4 hr each day for 3 consecutive days. This dosing protocol was lethal to over 60% of MT-null mice but did not kill any wild-type mice. More severe pulmonary damage was found by histopathological observation in MT-null mice than in wild-type mice. MT levels in the lung were elevated in wild-type mice after Hg0 vapor exposure, and gel filtration of the lung cytosol revealed that most of the mercury was associated with MT. In MT-null mice, MT levels were below the limit of detection (0.2 microg/g tissue) for the MT assay even after exposure. After exposure to Hg0 vapor for 3 consecutive days, the pulmonary mercury levels in wild-type mice were significantly higher than in MT-null mice. These findings suggest that MT plays a protective role against the acute pulmonary toxicity of Hg0 vapor.
本研究使用金属硫蛋白(MT)基因敲除小鼠和野生型小鼠,检测了金属硫蛋白(MT)对急性暴露于金属汞(Hg0)蒸气所致肺损伤的保护作用。两种品系的小鼠每天暴露于6.6至7.5 mg/m3的Hg0中,持续4小时,连续3天。该给药方案对超过60%的MT基因敲除小鼠是致命的,但未导致任何野生型小鼠死亡。组织病理学观察发现,MT基因敲除小鼠的肺损伤比野生型小鼠更严重。Hg0蒸气暴露后,野生型小鼠肺中的MT水平升高,对肺细胞质进行凝胶过滤显示,大部分汞与MT结合。在MT基因敲除小鼠中,即使在暴露后,MT水平也低于MT检测的检测限(0.2微克/克组织)。连续3天暴露于Hg0蒸气后,野生型小鼠肺中的汞水平显著高于MT基因敲除小鼠。这些发现表明,MT对Hg0蒸气的急性肺毒性具有保护作用。