Wang C, Brown S, Bhattacharyya M H
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Illinois 60439-4833.
Toxicol Appl Pharmacol. 1994 Aug;127(2):320-30. doi: 10.1006/taap.1994.1168.
To test whether Cd exposure would increase Ca release from bone during pregnancy and lactation in relation to the etiological mechanism of Itai-Itai disease, virgin female mice with 45Ca prelabeled skeletons (15 microCi/mouse) were subjected to one round of pregnancy/lactation and were exposed to a Ca-deficient diet containing 0, 5, or 25 ppm Cd or 25 ppm Pb for 32 days, from conception until Lactation Day 14. A striking loss of 45Ca was found in the dam's total skeleton (-40%), right femur (-47%), and lumbar vertebrae (L1-L5) (-75%) due only to pregnancy/lactation in conjunction with Ca deficiency. At both 5 and 25 ppm, Cd administered through food induced an additional significant 45Ca loss from the total skeleton (-25% at 5 ppm Cd, -30% at 25 ppm Cd) and right femur (39% at 5 ppm Cd, -32% at 25 ppm Cd) compared to 0 ppm animals. Almost all of the 45Ca lost from the dam's skeleton appeared in the pups, with 80% transferred via the dam's milk during lactation and only 20% transferred during gestation; a very small fraction of the dam's skeletal 45Ca was excreted. Considering stable Ca values, Cd exposure nearly doubled the loss of Ca from the dam's skeleton (-78 mg Ca/mouse at 0 ppm; -146 mg Ca/mouse at 5 and 25 ppm Cd). Paralleling 45Ca losses, a Ca-deficient diet in combination with pregnancy/lactation alone caused significant decreases in weight and mineral content of the right femur and lumbar vertebrae (dry weight, ash weight, ash/dry, Ca content, Ca/dry, and Ca/ash) (-8 to -52%). Cd at both 5 and 25 ppm showed additional decreases (-15 to -32%, Cd groups compared to 0 ppm animals). Responses were specific to Cd in that no significant effect occurred due to 32 days of Pb exposure (25 ppm). This experiment supports the view that Cd exposure in conjunction with Ca deficiency and pregnancy/lactation are key etiological factors of Itai-Itai disease and that Cd at both 5 and 25 ppm in conjunction with one round of gestation/lactation and Ca deficiency can induce an extreme demineralization characteristic of Itai-Itai-like syndrome.
为了检验镉暴露是否会在妊娠和哺乳期增加骨骼中的钙释放，这与痛痛病的病因机制有关，对预先用45钙标记骨骼（15微居里/只）的未孕雌性小鼠进行一轮妊娠/哺乳，并从受孕到哺乳第14天，使其暴露于含0、5或25 ppm镉或25 ppm铅的缺钙饮食中32天。仅由于妊娠/哺乳并伴有缺钙，发现母鼠的全身骨骼（-40%）、右股骨（-47%）和腰椎（L1-L5）（-75%）中的45钙显著流失。与0 ppm组动物相比，在5 ppm和25 ppm时，通过食物给予的镉会导致全身骨骼（5 ppm镉时为-25%，25 ppm镉时为-30%）和右股骨（5 ppm镉时为-39%，25 ppm镉时为-32%）中45钙进一步显著流失。母鼠骨骼中流失的几乎所有45钙都出现在幼崽中，其中80%在哺乳期间通过母鼠的乳汁转移，只有20%在妊娠期间转移；母鼠骨骼中极少量的45钙被排泄掉。考虑到稳定的钙值，镉暴露使母鼠骨骼中的钙流失几乎增加了一倍（0 ppm时为-78毫克钙/只；5 ppm和25 ppm镉时为-146毫克钙/只）。与45钙流失情况相似，仅缺钙饮食与妊娠/哺乳相结合会导致右股骨和腰椎的重量和矿物质含量（干重、灰重、灰分/干重、钙含量、钙/干重和钙/灰分）显著下降（-8%至-52%）。5 ppm和25 ppm的镉会导致进一步下降（与0 ppm组动物相比，镉组下降-15%至-32%）。这些反应对镉具有特异性，因为暴露于25 ppm铅32天没有产生显著影响。该实验支持以下观点：镉暴露与缺钙以及妊娠/哺乳是痛痛病的关键病因，5 ppm和25 ppm的镉与一轮妊娠/哺乳及缺钙相结合可诱发类似痛痛病综合征的极端脱矿质特征。
