Fowler B A, Woods J S
Lab Invest. 1977 Feb;36(2):122-30.
Ultrastructural morphometric and biochemical changes in liver mitochondria of fetal rats whose mothers were exposed to methyl mercury hydroxide in their drinking water at concentrations of 0, 3, 5, or 10 p.p.m. for 4 weeks prior to mating and through day 19 of pregnancy are described. A dose-related decrease in the volume density of mitochondria was observed in fetal hepatocytes of dams given the 5- and 10-p.p.m. dose levels. This finding was associated with decreased mitochondrial protein synthesis, which appeared to result primarily from decreased synthesis of mitochondrial structural proteins. Loss of respiratory control was observed in mitochondria from animals in the 3-p.p.m. dose group whereas state 3 respiration was abolished in animals exposed to the 5- and 10-p.p.m. dose levels. The specific activities of monoamine oxidase and cytochrome oxidase, outer and inner mitochondrial membrane marker enzymes respectively, showed dose-related decreases of up to 62 and 78 per cent of control, respectively. delta-Aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane, also showed dose-related decreases of up to 68 per cent of control. Malate dehydrogenase, a mitochondrial matrix marker enzyme, showed no change in activity at any dose level tested. These observations were correlated with dose-related tissue concentrations of methyl and inormpaired mitochondrial biogenesis and functional development is one basis for explaining the sensitivity of fetal animals to methyl mercury toxicity.
描述了在交配前4周及整个孕期第19天，其母鼠饮用含0、3、5或10 ppm氢氧化甲基汞的水的胎鼠肝脏线粒体的超微结构形态计量学和生化变化。在给予5 ppm和10 ppm剂量水平的母鼠所产胎鼠的肝细胞中，观察到线粒体体积密度呈剂量相关下降。这一发现与线粒体蛋白质合成减少有关，这似乎主要是由于线粒体结构蛋白合成减少所致。在3 ppm剂量组动物的线粒体中观察到呼吸控制丧失，而在暴露于5 ppm和10 ppm剂量水平的动物中，状态3呼吸被消除。单胺氧化酶和细胞色素氧化酶的比活性分别为线粒体外膜和内膜标记酶，显示出与剂量相关的下降，分别高达对照的62%和78%。与线粒体内膜松散结合的δ-氨基乙酰丙酸合成酶也显示出与剂量相关的下降，高达对照的68%。苹果酸脱氢酶是一种线粒体基质标记酶，在任何测试剂量水平下活性均无变化。这些观察结果与甲基的剂量相关组织浓度相关，线粒体生物发生受损和功能发育异常是解释胎鼠对甲基汞毒性敏感性的一个基础。
