Oberdörster G, Cherian M G, Baggs R B
Department of Environmental Medicine, University of Rochester, NY 14642.
Toxicol Lett. 1994 Jun;72(1-3):339-43. doi: 10.1016/0378-4274(94)90046-9.
There is sufficient evidence for pulmonary carcinogenicity of inhaled cadmium (Cd) compounds in rats whereas no such evidence was found in mice and hamsters, indicating significant species differences in the pulmonary response to inhaled Cd. We hypothesized that expression of metallothionein (MT) protein in the lung after inhalation of Cd differs between species thereby providing different degrees of sequestration of Cd and protection from its effects. Rats and mice were exposed to 100 micrograms CdCl2 aerosols/m3 for 4 weeks, and the presence of MT was determined in lung and free lung cell homogenates as well as by immunocytochemistry in lung sections up to 28 days post-exposure. Cd exposure significantly increased MT in homogenates of total lung in both species; however, no significant increase of MT in rat lung tissue after removal of free lung cells by lavage was found whereas MT was still significantly increased in lavaged mouse lung tissue throughout the post-exposure time. Histochemical analysis of lung sections revealed that mainly the epithelial cells of the bronchi, bronchioli and alveoli of Cd-exposed mice expressed MT. Baseline MT levels were also greater in the lungs of mice compared to rats. The retained Cd dose per g lung was about 2-fold greater in mice. The greater MT induction upon exposure to the same inhaled Cd concentration and the greater baseline MT levels may offer an explanation for the resistance of mice towards the pulmonary carcinogenic effect of inhaled Cd.
有充分证据表明吸入镉（Cd）化合物对大鼠具有肺致癌性，而在小鼠和仓鼠中未发现此类证据，这表明不同物种对吸入镉的肺部反应存在显著差异。我们推测，吸入镉后肺中金属硫蛋白（MT）的表达在不同物种间存在差异，从而对镉的螯合程度不同，对其影响的保护作用也不同。将大鼠和小鼠暴露于100微克/立方米的CdCl₂气溶胶中4周，并在暴露后长达28天的时间里，通过免疫细胞化学法在肺切片以及肺和游离肺细胞匀浆中检测MT的存在情况。镉暴露显著增加了两种动物全肺匀浆中的MT；然而，在通过灌洗去除游离肺细胞后，大鼠肺组织中的MT没有显著增加，而在整个暴露后时间里，灌洗后的小鼠肺组织中的MT仍显著增加。肺切片的组织化学分析显示，镉暴露小鼠的支气管、细支气管和肺泡的上皮细胞主要表达MT。与大鼠相比，小鼠肺中的基线MT水平也更高。每克肺中保留的镉剂量在小鼠中约高2倍。在暴露于相同吸入镉浓度时MT诱导程度更高以及基线MT水平更高，可能解释了小鼠对吸入镉的肺致癌作用具有抗性的原因。
