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The effect of oxythioquinox exposure on normal human mammary epithelial cell gene expression: a microarray analysis
Maureen R Gwinn1, Diana L Whipkey, Ainsley Weston
1Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Mail Stop #L-2015, Morgantown, WV 26505-2888, USA. mwg9@cdc.gov
Environmental Health : a Global Access Science Source
|September 25, 2004
Summary
Inter-individual variation in human mammary cells impacts gene expression signatures after oxythioquinox (OTQ) exposure. These gene expression patterns may identify populations susceptible to cancer risk.
Area of Science:
- Toxicogenomics
- Human cell biology
- Biomarker discovery
Background:
- Limited understanding of inter-individual variation in human cellular responses to chemical exposure.
- Gene expression signatures are typically derived from animal models, lacking human variability data.
- Focus on inter-individual differences in gene expression signatures in normal human mammary epithelial cells (NHMECs).
Purpose of the Study:
- To investigate inter-individual variations in gene expression profiles of NHMECs exposed to oxythioquinox (OTQ).
- To identify potential biomarkers for cancer risk based on differential gene expression.
- To explore the influence of p53 polymorphisms on cellular response to OTQ.
Main Methods:
- Primary NHMECs from four women were exposed to OTQ.
- Gene expression analyzed using high-density oligonucleotide DNA microarrays (HuGeneFL, Affymetrix).
- Changes verified by real-time polymerase chain reaction (ABI); data analyzed for genes altered by signal log ratio (SLR) +/- 0.6 and p < 0.05.
Main Results:
- OTQ exposure altered gene expression in NHMECs, with only 36 genes consistently affected across cell strains.
- Significant differences observed in gene expression patterns between NHMEC strains with different p53 polymorphisms.
- Cells with major p53 variant showed 83 common altered genes; intermediate variant strains showed 105 common altered genes.
Conclusions:
- Differential gene expression patterns in response to OTQ may serve as biomarkers for inter-individual variation in cancer risk.
- Identifying specific gene expression profiles can help pinpoint susceptible populations.
- This study highlights the importance of considering human variability in toxicological assessments.