Mahaffey K R, Capar S G, Gladen B C, Fowler B A
J Lab Clin Med. 1981 Oct;98(4):463-81.
Male rats were exposed to dietary Pb (200 ppm), Cd (50 ppm), or As (50 ppm) as arsenate either alone or in combination for 10 weeks using a 2 x 2 x 2 factorial design. Cd and As reduced weight gain even when differences in food intake were taken into account, and administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased RBCs were observed after administration of Pb, Cd, or As, and more cells were observed when two or three metals were concomitantly administered. Despite increased numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination. Analysis of blood chemistries showed normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, but not by Cd or As. SGOT activity was reduced by As alone. Serum alkaline phosphatase was reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, but Cd or As alone or in combination had no effect. Liver weight/body weight ratios were reduced in animals fed Cd. Kidney histology showed predominantly Pb effects, i.e., intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies and mitochondrial swelling. Concurrent administration of Cd reduced total mean bone and kidney Pb levels by 50% and 60%, respectively, and this was associated with a decrease in kidney intranuclear inclusions. Cd exposure also reduced renal, femur, and liver concentrations of Fe by 33%, 43%, and 63%, respectively, decreased femur Zn by 27%, but increased renal Zn by 20%. Administration of As produced mild swelling of tubule cell mitochondria, increased mean total renal Cu to 200% of control, and increased liver Fe by 44%. Dietary Pb produced increased urinary excretion of ALA and coproporphyrin. Dietary exposure to As caused increased urinary excretion of uroporphyrin and to a lesser extent coproporphyrin, whereas dietary Cd caused no significant changes in urinary levels of any of the porphyrins measured. Pb plus As produced an additive effect on coproporphyrin excretion but not that of ALA or uroporphyrin. These studies indicate that interactions between common toxic elements do occur and are characterized by alterations in both tissue trace metal levels and toxicity.
采用2×2×2析因设计，将雄性大鼠单独或联合暴露于含200 ppm铅、50 ppm镉或50 ppm砷酸盐的饮食中10周。即使考虑到食物摄入量的差异，镉和砷仍会降低体重增加，同时给予镉和砷比单独给予任何一种金属更能抑制体重增加。铅对食物消耗或体重增加没有不利影响。给予铅、镉或砷后观察到红细胞增多，同时给予两种或三种金属时观察到更多的细胞。尽管循环红细胞数量增加，但血红蛋白和血细胞比容降低，尤其是铅 - 镉联合组。血液化学分析显示血尿素氮、肌酐、胆固醇、钙、白蛋白、总蛋白和胆红素在正常范围内。尿酸因铅而升高，但镉或砷不会使其升高。仅砷会降低谷草转氨酶活性。砷或镉会降低血清碱性磷酸酶，但铅不会。砷和镉的组合不会进一步降低该酶的活性。仅铅会增加肾脏重量和肾脏重量/体重比，而单独的镉或砷或它们的组合没有影响。喂食镉的动物肝脏重量/体重比降低。肾脏组织学主要显示铅的影响，即核内包涵体和混浊肿胀。对铅处理动物的肾脏进行超微结构评估发现核包涵体和线粒体肿胀。同时给予镉可使骨骼和肾脏中的总铅平均水平分别降低50%和60%，这与肾脏核内包涵体的减少有关。镉暴露还分别使肾脏、股骨和肝脏中的铁浓度降低33%、43%和63%，使股骨锌降低27%，但使肾脏锌增加20%。给予砷会使肾小管细胞线粒体轻度肿胀，使肾脏总铜平均增加至对照的200%，并使肝脏铁增加44%。饮食中的铅会增加δ-氨基乙酰丙酸和粪卟啉的尿排泄量。饮食中接触砷会导致尿卟啉排泄增加，粪卟啉排泄增加程度较小，而饮食中的镉对所测任何卟啉的尿水平均无显著影响。铅加砷对粪卟啉排泄有相加作用，但对δ-氨基乙酰丙酸或尿卟啉排泄没有相加作用。这些研究表明，常见有毒元素之间确实会发生相互作用，其特征是组织中微量金属水平和毒性的改变。
