Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice
Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice
复制标题
DOI：
10.1016/s0006-2952(01)00752-3
复制
发表时间：
2001-10-15
影响因子：
5.8
通讯作者：
DePierre, JW
中科院分区：
文献类型：
--
作者：
Yang, Q;Xie, Y;DePierre, JW
我们最近证明，在用强效过氧化物酶体增殖剂（PP），如全氟辛酸（PFOA）、WY-14，643、萘诺平和邻苯二甲酸二（2-乙基己基）酯（DEHP）对小鼠进行饮食治疗后，会发生严重的胸腺和脾脏萎缩。在本研究中，我们进一步研究了这种现象，采用相对惰性的PP，PFOA。剂量依赖性和时间过程的比较表明，过氧化物酶体增殖效应发生在胸腺和脾脏萎缩之前。然而，在从饮食中撤出PFOA后，胸腺和脾脏的重量分别在10天和5天内迅速恢复正常，与更持久的过氧化物酶体增殖相反。此外，在全氟辛酸处理和随后从饮食中撤出后，胸腺和脾脏重量的变化分别抵消了总胸腺细胞和脾细胞计数的变化。以前发现，在PFOA处理后，S和G2/M期的胸腺细胞群以及CD 4（+）CD 8（+）细胞数量的减少最为显著，这可能反映了与胸腺细胞发育相关的胸腺细胞增殖抑制。在这里，胸腺细胞的恢复开始于细胞周期的这些相同阶段的群体的增加，其中CD 4（+）CD 8（+）细胞恢复最快，进一步支持了我们先前的假设。PP的这些免疫毒性作用的变化，他们在脂肪酸代谢引起的可能关系进行了讨论。(C)2001 Elsevier Science Inc. All rights reserved.
We recently demonstrated that severe thymic and splenic atrophy occur upon dietary treatment of mice with potent peroxisome proliferators (PPs), e.g. perfluorooctanoic acid (PFOA), WY-14,643, nafenopin, and di(2-ethylhexyl)phthalate (DEHP). In the present study, we investigated this phenomenon further employing a relative inert PP, PFOA. Comparison of the dose-dependencies and time-courses indicated that the peroxisome proliferative effect occurred prior to atrophy of both the thymus and spleen. However, following withdrawal of PFOA from the diet, the weight of the thymus and spleen rapidly returned to normal within 10 and 5 days, respectively, in contrast to the more persistent peroxisome proliferation. Furthermore, the changes in thymus and spleen weight upon PFOA treatment and the following withdrawal from diet paralleled the changes in total thymocyte and splenocyte counts, respectively. It was found previously that the decreases in the thymocyte populations present in the S and G2/M phases, as well as in the number of CD4(+)CD8(+) cells upon PFOA treatment, were the most dramatic, perhaps reflecting inhibition of thymocyte proliferation in connection with thymocyte development. Here, the recovery of thymocytes began with increases in the populations in these same phases of the cell cycle, with CD4(+)CD8(+) cells recovering most rapidly, lending further support to our previous hypothesis. The possible relationship of these immunotoxic effects of PPs to the changes they cause in fatty acid metabolism is discussed. (C) 2001 Elsevier Science Inc. All rights reserved.