J Appl Toxicol. 2009 Oct;29(7):569-77. doi: 10.1002/jat.1441.
cDNA micorarray approach was applied to hepatic transcriptional profile analysis in male mouse (Mus musculus, ICR) to assess the potential health effects of drinking water in Nanjing, China. Mice were treated with continuous exposure to drinking water for 90 days. Hepatic gene expression was analyzed with Affymetrix Mouse Genome 430A 2.0 arrays, and pathway analysis was carried out by Molecule Annotation System 2.0 and KEGG pathway database. A total of 836 genes were found to be significantly altered (1.5-fold, P < or = 0.05), including 294 up-regulated genes and 542 down-regulated genes. According to biological pathway analysis, drinking water exposure resulted in aberration of gene expression and biological pathways linked to xenobiotic metabolism, signal transduction, cell cycle and oxidative stress response. Further, deregulation of several genes associated with carcinogenesis or tumor progression including Ccnd1, Egfr, Map2k3, Mcm2, Orc2l and Smad2 was observed. Although transcription changes in identified genes are unlikely to be used as a sole indicator of adverse health effects, the results of this study could enhance our understanding of early toxic effects of drinking water exposure and support future studies on drinking water safety.
采用 cDNA 微阵列方法分析雄性小鼠(ICR)肝脏转录组谱,以评估中国南京饮用水的潜在健康影响。将小鼠连续暴露于饮用水中 90 天。使用 Affymetrix Mouse Genome 430A 2.0 阵列分析肝基因表达,并通过分子注释系统 2.0 和 KEGG 途径数据库进行途径分析。共发现 836 个基因表达显著改变(1.5 倍,P < 或 = 0.05),包括 294 个上调基因和 542 个下调基因。根据生物途径分析,饮用水暴露导致与外源物质代谢、信号转导、细胞周期和氧化应激反应相关的基因表达和生物途径异常。此外,还观察到与致癌或肿瘤进展相关的几个基因(如 Ccnd1、Egfr、Map2k3、Mcm2、Orc2l 和 Smad2)的表达失调。虽然鉴定基因的转录变化不太可能用作不良健康影响的唯一指标,但本研究结果可以增强我们对饮用水暴露早期毒性作用的理解,并支持未来对饮用水安全的研究。