Early whole-genome transcriptional response induced by benzo[a]pyrene diol epoxide in a normal human cell line.
(+/-)-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.
Lu
Xiangyun
X
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Shao
Jimin
J
Li
Hongjuan
H
Yu
Yingnian
Y
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic
D002273:Carcinogens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide