Role of inflammatory cytokines and DNA damage repair proteins in sulfur mustard exposed mice liver
Role of inflammatory cytokines and DNA damage repair proteins in sulfur mustard exposed mice liver
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DOI：
10.1080/15376510902903766
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发表时间：
2009-06-01
影响因子：
3.2
通讯作者：
Bhattacharya, B. K.
中科院分区：
文献类型：
--
作者：
Anand, T.;Vijayaraghavan, R.;Bhattacharya, B. K.
硫芥（双（2-氯乙基）硫醚）是一种烷化剂，会在皮肤上产生水泡，并引起全身毒性和 DNA 链断裂。在硫芥 (SM) 暴露的小鼠肝脏中研究了炎症细胞因子、受体和 DNA 损伤信号通路特定基因的机制和作用。雌性小鼠经皮暴露于 1.0 L.DS0 的 SM（8.1 mg/kg 体重）。在暴露于 SM 后第 1 天和第 3 天测定炎症细胞因子基因表达谱，并通过 DNA 微阵列和半定量逆转录聚合酶链式反应 (RT-PCR) 检查第 1、3 和 7 天的 DNA 损伤信号通路特异性、双链断裂修复蛋白基因表达谱。抗炎细胞因子和受体从第 1 天到第 3 天下调。促炎基因 TNF-α、TNF 受体从第 1 天到第 3 天上调。双链 DNA 断裂修复蛋白 Rad23、Rac50、Rad51、Rad52 和 Rad541 从第 1 天到第 7 天下调。该结果表明硫芥引起炎症反应，激活信号转导途径中的级联事件，并且促进染色体 DNA 中不可逆的双链 DNA 断裂，从而导致细胞死亡。
Sulfur mustard (bis-(2-chloroethyl) sulfide) is an alkylating agent, and produces blisters on skin and causes systemic toxicity and DNA strand breaks. The mechanism and role of inflammatory cytokines, receptors, and DNA damage signaling pathway specific genes were studied in sulfur mustard (SM) exposed mouse liver. Female mice were exposed percutaneously with 1.0 L.DS0 of SM (8.1 mg/kg body weight). Inflammatory cytokine gene expression profiles were determined at I and 3 days post-exposure to SM and DNA damage signaling pathway specific, double strand break repair proteins gene expression profile at 1, 3, and 7 days were examined by DNA microarrays and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Anti-inflammatory cytokines and receptors were down-regulated from day 1 to day 3. Pro-inflammatory genes TNF-alpha, TNF receptors were up-regulated from day 1 to day 3. Double strand DNA break repair proteins Rad23, Rac50, Rad51, Rad52, and Rad541 were down-regulated from day 1 to day 7. This result indicates sulfur mustard causes inflammatory response, activates the cascade of events in the signal transduction pathway, and promotes irreversible double strand DNA breaks in chromosomal DNA, which is leading to cell death.