Suppression of Radiation-Induced Testicular Germ Cell Apoptosis by 2,5-Hexanedione Pretreatment. II. Gene Array Analysis Reveals Adaptive Changes in Cell Cycle and Cell Death Pathways
Suppression of Radiation-Induced Testicular Germ Cell Apoptosis by 2,5-Hexanedione Pretreatment. II. Gene Array Analysis Reveals Adaptive Changes in Cell Cycle and Cell Death Pathways
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DOI：
10.1093/toxsci/kfq204
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发表时间：
2010-10-01
影响因子：
3.8
通讯作者：
Boekelheide, Kim
中科院分区：
文献类型：
--
作者：
Campion, Sarah N.;Houseman, E. Andres;Boekelheide, Kim
支持细胞是睾丸生殖细胞维持和存活所必需的。我们意外地观察到，X射线(x射线)诱导的生殖细胞损失通过与Sertoli细胞毒物2，5-己二酮(HD)共同暴露而减弱。随着支持细胞支持的减少，生殖细胞凋亡减少的潜在机制尚不清楚。目前的研究是为了检测HD和x射线共同暴露时睾丸基因表达的变化。成年雄性大鼠暴露于饮水中的HD(0.33或1%)18d后再接受X射线(2或5Gy射线照射)，共设9个处理组。3h后取睾丸组织，用Affymetrix大鼠基因组2302.0芯片分析总信使RNA。使用LIMMA分析归一化的log2表达值，并使用线性对比进行总结，该对比旨在总结所有治疗组中HD的聚集效应，超过X射线改变。将这些对比与X射线的整体线性趋势表达进行比较，以确定HD效应对于X射线损伤是激励性的还是拮抗性的。进行过度表达分析，以确定HD基因表达修饰最大的生物途径。HD对细胞周期和细胞死亡/凋亡相关基因有显著影响。这项研究的结果通过分析HD和X射线联合暴露对基因表达的影响，揭示了HD和X射线联合暴露后生殖细胞毒性减弱的机制，并表明HD预暴露降低了支持细胞支持的生殖细胞增殖，从而降低了生殖细胞对X射线的易感性。
Sertoli cells are essential for testicular germ cell maintenance and survival. We made the unexpected observation that x-radiation (x-ray)-induced germ cell loss is attenuated by co-exposure with the Sertoli cell toxicant 2,5-hexanedione (HD). The mechanisms underlying this attenuation of germ cell apoptosis with reduced Sertoli cell support are unknown. The current study was performed to examine alterations in testicular gene expression with co-exposure to HD and x-ray. Adult male rats were exposed to HD (0.33 or 1%) in the drinking water for 18 days followed by x-ray (2 or 5 Gy), resulting in nine treatment groups. Testis samples were collected after 3 h and total messenger RNA was analyzed using Affymetrix Rat Genome 230 2.0 arrays. Normalized log2-expression values were analyzed using LIMMA and summarized using linear contrasts designed to summarize the aggregated effect, in excess of x-ray alteration, of HD across all treatment groups. These contrasts were compared with the overall linear trend expression for x-ray, to determine whether HD effects were agonistic or antagonistic with respect to x-ray damage. Overrepresentation analysis to identify biological pathways where HD modification of gene expression was the greatest was performed. HD exerted a significant influence on genes involved in cell cycle and cell death/apoptosis. The results of this study provide insight into the mechanisms underlying attenuated germ cell toxicity following HD and x-ray co-exposure through the analysis of co-exposure effects on gene expression, and suggest that HD pre-exposure reduces Sertoli cell supported germ cell proliferation thereby reducing germ cell vulnerability to x-rays.