Differential Gene Expression in Normal Human Mammary Epithelial Cells Treated with Malathion Monitored by DNA Microarrays Maureen R. Gwinn,1 Diana L. Whipkey,2 Lora B. Tennant,2 and Ainsley Weston2 1Pathology and Physiology Branch, and 2Molecular Epidemiology Team, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, USA Abstract 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. Key words: DNA microarray, gene expression, malathion, pesticide, toxicology. Environ Health Perspect 113:1046-1051 (2005) . doi:10.1289/ehp.7311 available via http://dx.doi.org/ [Online 10 May 2005] Address correspondence to A. Weston, Molecular Epidemiology Team, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, NIOSH, CDC, 1095 Willowdale Rd., Mail Stop L-3014, Morgantown, WV 26505-2888 USA. Telephone: (304) 285-6221. Fax: (304) 285-5708. E-mail: agw8@cdc.gov We thank M. Toraason and L. Sargent for their careful review of the manuscript. We also thank G. Johnson for her invaluable assistance in formatting and editing the manuscript. The authors declare they have no competing financial interests. Received 7 June 2004 ; accepted 10 May 2005. The full version of this article is available for free in HTML or PDF formats. |