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Temporal gene expression changes induced by a low concentration of benzo[a]pyrene diol epoxide in a normal human cell
Xiangyun Lu1, Jimin Shao, Hongjuan Li
1Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Abstract:
(+ 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.
Insights
This study reveals how normal human cells respond to carcinogen BPDE over time, identifying key gene expression changes related to DNA damage, cell cycle, and survival. These findings offer insights into BPDE-induced mutagenesis and carcinogenesis.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Genomics
Background:
- Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a known ultimate carcinogen causing bulky DNA adducts.
- Understanding the cellular response to low-dose carcinogen exposure is crucial for assessing risk.
Purpose of the Study:
- To investigate the temporal transcriptomic response of normal human cells to low-dose BPDE exposure.
- To identify dynamic gene expression patterns indicative of cellular damage, progression, and recovery.
Main Methods:
- Affymetrix HG-U133 Plus 2.0 microarray analysis.
- Quantitative real-time RT-PCR (qRT-PCR).
- In silico genomic data comparison.
Main Results:
- Significant differential gene expression was observed at 1, 10, and 22 hours post-BPDE exposure.
- Gene expression dynamics reflected a cellular response from damage initiation to recovery, including cell cycle inhibition and subsequent survival.
- BPDE and UV exposure induced common transcriptional responses, suggesting shared molecular pathways.
Conclusions:
- A time-course transcriptional signature of low-dose BPDE exposure in human cells was identified.
- The findings contribute to understanding the complex mechanisms of mutagenesis and carcinogenesis driven by BPDE.
- Dynamic gene regulation patterns correlate with observed cell cycle arrest and cytotoxicity.
