Lu Xiangyun, Shao Jimin, Li Hongjuan, Yu Yingnian
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Genomics. 2009 Apr;93(4):332-42. doi: 10.1016/j.ygeno.2008.12.007. Epub 2009 Jan 14.
(+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogen causing bulky-adduct DNA damage. In this study, we investigated early transcriptional signatures induced by various concentrations (0.005, 0.05, and 0.5 microM) of this carcinogen in a normal human cell line (FL human amnion epithelial cells) using the whole-genome Affymetrix HG-U133 Set microarray. The numerous identified genes were involved in multiple functions and higher doses of BPDE elicited more robust expression changes. The disturbance of genes involved in cell cycle regulation, growth and apoptosis was correlated with the S and G(2)/M phase cell cycle arrest and cytotoxic phenotypes induced by different levels of BPDE. Bioinformatic analysis showed that several transcription factors and their related stress signaling pathways might partly account for the transcriptional signature induced by BPDE. Additionally, gene ontology analysis of the microarray data showed down-regulation of transport, cytoskeleton and DNA repair by 0.5 microM BPDE exposure. In conclusion, this genomic analysis helps to understand the mechanism of cellular response to BPDE.
（±）-反式苯并[a]芘-7,8-二醇-9,10-环氧化物（BPDE）是一种可导致DNA大分子加合物损伤的致癌物。在本研究中，我们使用全基因组Affymetrix HG-U133 Set微阵列，调查了该致癌物在正常人细胞系（FL人羊膜上皮细胞）中不同浓度（0.005、0.05和0.5微摩尔）诱导的早期转录特征。大量鉴定出的基因涉及多种功能，且更高剂量的BPDE引发更显著的表达变化。参与细胞周期调控、生长和凋亡的基因的紊乱与不同水平的BPDE诱导的S期和G2/M期细胞周期阻滞及细胞毒性表型相关。生物信息学分析表明，几种转录因子及其相关的应激信号通路可能部分解释了BPDE诱导的转录特征。此外，对微阵列数据的基因本体分析显示，0.5微摩尔BPDE暴露会导致转运、细胞骨架和DNA修复功能下调。总之，这种基因组分析有助于理解细胞对BPDE的反应机制。
