Differential Gene Expression in Normal Human Mammary Epithelial Cells Treated with Malathion Monitored by DNA Microarrays

Details

• Alternative Title:
  Environ Health Perspect
• Personal Author:
  Gwinn, Maureen R. ; Whipkey, Diana L. ; Tennant, Lora B. ; Weston, Ainsley
• Description:
  Organophosphate pesticides are a major source of occupational exposure in the United States. Moreover, malathion has been sprayed over major urban populations in an effort to control mosquitoes carrying West Nile virus. Previous research, reviewed by the U.S. Environmental Protection Agency, on the genotoxicity and carcinogenicity of malathion has been inconclusive, although malathion is a known endocrine disruptor. Here, interindividual variations and commonality of gene expression signatures have been studied in normal human mammary epithelial cells from four women undergoing reduction mammoplasty. The cell strains were obtained from the discarded tissues through the Cooperative Human Tissue Network (sponsors: National Cancer Institute and National Disease Research Interchange). Interindividual variation of gene expression patterns in response to malathion was observed in various clustering patterns for the four cell strains. Further clustering identified three genes with increased expression after treatment in all four cell strains. These genes were two aldo-keto reductases (AKR1C1 and AKR1C2) and an estrogen-responsive gene (EBBP). Decreased expression of six RNA species was seen at various time points in all cell strains analyzed: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1), and a gene of unknown function (GenBank accession no. AI859865). Expression changes in all these genes, detected by DNA microarrays, have been verified by real-time polymerase chain reaction. Differential changes in expression of these genes may yield biomarkers that provide insight into interindividual variation in malathion toxicity.
• Subjects:
  DNA Microarray Epithelial Cells Female Gene Expression Gene Expression Profiling Gene Expression Regulation Humans Insecticides Malathion Mammary Glands, Human Oligonucleotide Array Sequence Analysis Pesticide Research Toxicology

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• Source:
  Environ Health Perspect. 2005; 113(8):1046-1051.
• Document Type:
  Journal Article
• Volume:
  113
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b8aa8e41e97d1c307041485158edab0d39642d4313f802973614953a457bd340
• Download URL:
  https://stacks.cdc.gov/view/cdc/3864/cdc_3864_DS1.pdf
• File Type:
  [PDF - 118.02 KB ]