Differential gene expression in normal human mammary epithelial cells treated with malathion monitored by DNA microarrays.
Gwinn-MR; Whipkey-DL; Tennant-LB; Weston-A
Environ Health Perspect 2005 Aug; 113(8):1046-1051
Organophosphate pesticides represent a major occupational exposure in the United States. Moreover, malathion has been sprayed over major urban populations in an effort to control mosquitos carrying West Nile Virus. Previous research, reviewed by the Environmental Protection Agency, on the genotoxicity and carcinogenicity of malathion has been inconclusive, although malathion is a known endocrine disruptor. Here inter-individual 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). Inter-individual variation of gene expression patterns in response to malathion was observed in various clustering patterns for the four cell strains. Further clustering identified 3 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, these were: 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 number AI859865). Expression changes in all these genes, detected by DNA microarrays, have been verified by real-time PCR. Differential changes in expression of these genes may yield biomarkers that provide insight into inter-individual variation in malathion toxicity.
Genes; Pesticides; Organo-phosphorus-pesticides; Occupational-exposure; Insecticides; Insects; Genotoxic-effects; Carcinogenicity; Biomarkers; Toxins
Pathology and Physiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, MS 2015, Morgantown, WV 26505-2888
Environmental Health Perspectives