Bagchi D, Bhattacharya G, Stohs S J
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Toxicology. 1996 Aug 1;112(1):57-68. doi: 10.1016/0300-483x(96)03350-1.
The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydrocarbons endrin and chlordane and the organophosphate pesticides chlorpyrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanism involved in the induction of oxidative stress by these xenobiotics is unknown. No information is available regarding whether these pesticides can induce the expression of heat shock (stress) protein (Hsp) genes as a common protective mechanism against tissue damage. The pesticides were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h. The animals were killed at 24 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a separate series of experiments, cultured neuroactive PC-12 cells were treated 24 h with 50, 100 or 200 nM concentrations of these pesticides. Alachlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp89 beta in hepatic and brain tissues, as well as in cultured PC-12 cells. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis using Hsp90 antibody. Except chlordane all these pesticides induced enhanced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by the pesticides which were used, and demonstrate that these pesticides can induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against oxidative stress induced by structurally diverse pesticides.
氯乙酰胺类杀虫剂甲草胺、多卤代环状烃类化合物异狄氏剂和氯丹以及有机磷酸酯类杀虫剂毒死蜱和倍硫磷可诱导氧化组织损伤效应，包括脂质过氧化和核DNA单链断裂。这些外源性物质诱导氧化应激的机制尚不清楚。关于这些农药是否能诱导热休克（应激）蛋白（Hsp）基因表达作为一种针对组织损伤的常见保护机制，目前尚无相关信息。将这些农药分别以两个0.25 LD50剂量经口给予雌性Sprague-Dawley大鼠，给药时间分别为0小时和21小时。在24小时时处死动物，取出肝脏、大脑、心脏和肺组织，通过蛋白质免疫印迹法和Northern印迹分析法检测Hsps的诱导情况。在另一系列实验中，用50、100或200 nM浓度的这些农药处理培养的神经活性PC-12细胞24小时。甲草胺、异狄氏剂、毒死蜱和倍硫磷在肝脏和脑组织以及培养的PC-12细胞中诱导Hsp89α和Hsp89β表达。氯丹在处理大鼠的肝脏和脑组织中诱导了一些Hsp89α的表达，但未诱导Hsp89β的表达。在异狄氏剂和甲草胺处理动物的肺组织中观察到了一些Hsp89β的表达。使用Hsp90抗体的蛋白质免疫印迹分析证实了这些发现。除氯丹外，所有这些农药在培养的PC-12细胞中均诱导Hsp90的合成增加。结果表明，所使用的农药诱导的Hsps模式存在显著的组织差异，并证明这些农药可在大鼠的各种靶器官中诱导Hsp89α和Hsp89β基因的表达。这些结果支持了这样一种假设，即这些基因可能在机制上参与保护组织免受结构多样的农药诱导的氧化应激。
