Temporal gene expression changes induced by a low concentration of benzo[a]pyrene diol epoxide in a normal human cell line.
(+ or -)-anti-Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), which causes bulky-adduct DNA damage, is well-characterized as the ultimate carcinogen of benzo[a]pyrene (BaP). In this study, we have employed Affymetrix HG-U133 Plus 2.0 microarray and quantitative real-time RT-PCR methods to investigate a temporal transcriptomic response triggered by a low concentration (0.05 microM) of BPDE at 1, 10, and 22 h after exposure in normal human cells. The differential gene expression profiles at the three time points varied greatly, and generally reflected a cellular responsive process from initiation to progression and to recovery after the BPDE-caused damage. The dynamic regulation of the genes related with cell cycle progression and cell fate exhibited a tendency from inhibition to survival, which was accordant with the cell cycle arrest and cytotoxicity data induced by the low-dose BPDE exposure. In silico comparison of the genomic data revealed that BPDE and ultraviolet induced a panel of common transcriptional responses, which might be related with a series of similar molecular processes elicited by these two DNA-damaging agents. In conclusion, this whole-genome time-course study has identified a dynamically regulated transcriptional signature after low-dose BPDE exposure, which may help to understand the complex mechanisms of mutagenesis and carcinogenesis induced by 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 / Q000008:administration & dosage*; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009153:Mutagens / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014466:Ultraviolet Rays
D009153:Mutagens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide