de la Rosa Patricia, Barnett John B, Schafer Rosana
NIOSH-HELD-ASB, Morgantown, West Virginia, USA.
J Toxicol Environ Health A. 2005 Jan 22;68(2):81-98. doi: 10.1080/15287390590886072.
3,4-Dichloropropionanilide (propanil) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two commonly used herbicides that are marketed as a chemical mixture. It was hypothesized that the interaction between these two herbicides, when administered as a mixture, would result in a greater effect on the immune system than the individual components of the mixture. The present study demonstrates in a murine model that a mixture of propanil and 2,4-D, when compared to single herbicide exposures, exacerbates decreases in thymocyte populations 2 d postexposure and inhibits the repopulation of T-cells in the thymus 7 d postexposure. Exposure to 150 mg herbicide/kg body weight of propanil or 2,4-D alone had no effect on thymus weight. In contrast, decreases in the ratio of thymus weight to body weight (TW:BW) occurred 2 d after treatment with the mixture of 150 mg propanil/kg body weight + 150 mg 2,4-D/kg body weight (150/150). Thymic atrophy was associated with a decrease in the double-positive thymocyte population (CD4+CD8+) and correlated with sera corticosterone levels from 600 to 1000 pg/ml. Therefore, the hypothesis was tested that glucocorticoids, induced after exposure to herbicides, were responsible for the thymic atrophy and depletion of thymocytes. However, similar levels of corticosterone were induced after exposure to 50, 100, or 150 mg propanil/kg body weight, and 50/50 or 100/100 mixture treatments, doses that did not produce thymic atrophy or cell loss. In addition, RU 486, a glucocorticoid receptor blocker, only partially abrogated the thymic atrophy in mice exposed to the 150/150 mixture of herbicides. These results suggest that glucocorticoids are only partially responsible for herbicide-induced thymic atrophy. This study demonstrates that the effects of exposure to a mixture of chemicals cannot always be predicted based on single exposure data and emphasizes the importance of mixture-based studies.
3,4-二氯丙酰苯胺（敌稗）和2,4-二氯苯氧乙酸（2,4-D）是两种常用除草剂，以化学混合物形式销售。据推测，这两种除草剂混合使用时，其相互作用对免疫系统产生的影响会比混合物中的单个成分更大。本研究在小鼠模型中表明，与单独接触单一除草剂相比，敌稗和2,4-D的混合物在接触后2天会加剧胸腺细胞数量的减少，并在接触后7天抑制胸腺中T细胞的重新增殖。单独接触150毫克/千克体重的敌稗或2,4-D对胸腺重量没有影响。相比之下，用150毫克/千克体重的敌稗 + 150毫克/千克体重的2,4-D（150/150）混合物处理后2天，胸腺重量与体重之比（TW:BW）降低。胸腺萎缩与双阳性胸腺细胞群体（CD4+CD8+）的减少有关，并且与血清皮质酮水平在600至1000皮克/毫升之间相关。因此，对以下假设进行了检验：接触除草剂后诱导产生的糖皮质激素是胸腺萎缩和胸腺细胞耗竭的原因。然而，接触50、100或150毫克/千克体重的敌稗以及50/50或100/100混合物处理后，诱导产生的皮质酮水平相似，而这些剂量并未导致胸腺萎缩或细胞损失。此外，糖皮质激素受体阻滞剂RU 486仅部分消除了接触150/150除草剂混合物小鼠的胸腺萎缩。这些结果表明，糖皮质激素只是除草剂诱导胸腺萎缩的部分原因。本研究表明，接触化学混合物的影响不能总是根据单一接触数据来预测，并强调了基于混合物研究的重要性。
Zotero 插件