Slotkin T A, Kavlock R J, Cowdery T, Orband L, Bartolome M, Gray J A, Rehnberg B F, Bartolome J
Toxicol Lett. 1986 Dec;34(2-3):231-45. doi: 10.1016/0378-4274(86)90215-8.
The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions of urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. In addition, the reactivity of the kidney to challenge with desmopressin was altered coincidentally with the appearance of the effects on basal clearance mechanisms. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs. postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.
在发育中的大鼠身上研究了产前暴露于甲基汞对肾和肝反应系统功能发育的影响。甲基汞使肾鸟氨酸脱羧酶（ODC，一种参与细胞成熟调节的酶）的基础活性升高，并最终导致相对肥大；肝脏ODC活性降低，肥大不明显。相反，产前暴露于甲基汞会显著增强肝脏ODC对营养刺激物（血管加压素、异丙肾上腺素）的反应性，而肾脏ODC反应受影响较小（血管加压素）或实际上降低（异丙肾上腺素）。甲基汞对肾脏排泄功能的靶向作用也很突出，尿素和电解质的排泄分数增加，最终通过肌酐清除率评估肾小球滤过率降低。此外，肾脏对去氨加压素刺激的反应性改变与对基础清除机制的影响同时出现。这些研究表明，通常与对神经行为模式发育的选择性作用相关的甲基汞剂量也会影响其他器官系统的功能个体发育；此外，产前和产后甲基汞暴露的靶组织不同，这表明甲基汞的功能致畸学表现出关键的敏感时期。
