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Alteration of gene expression in human cells treated with the agricultural chemical diazinon: possible interaction in fetal development

R Hokanson

R Fudge

R Chowdhary

Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA

D Busbee

Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA dbusbee{at}cvm.tamu.edu; Department of Environmental and Industrial Health, School of Rural Public Health, TAMU Health Science Center, Texas A&M University, College Station, TX 77843, USA

Agricultural chemicals frequently alter human health or development, typically because they have endocrine agonist or antagonist activities and alter hormone-regulation of gene expression. The insecticide, diazinon, was evaluated for gene expression disrupting activity using MCF-7 cells, an estrogen-dependent human cell line, to examine the capacity of the insecticide to disrupt gene expression essential for morphological development, immune system development or function, and/or central nervous system development and function. MCF-7 cells were treated with 30, 50 or 67 ppm diazinon, and gene expression was measured in treated cells compared to expression in untreated or estrogen-treated cells. DNA microarray analysis of diazinon-treated cells showed significant upor down-regulation of a large number of genes compared to untreated cells. Of the 600 human genes on the Phase 1 chip utilized for these studies, two specific genescalreticulin and TGF-b3were selected for corroboration using quantitative real time PCR (qrtPCR). qrtPCR, completed to assess gene expression levels for calreticulin and TGFb3, confirmed results showing significant up-regulation of these two genes obtained from the microarray data. These studies were designed to provide baseline data on the gene expressionaltering capacity of a specific chemical, diazinon, and allow a partial assessment of the potentially deleterious effects associated with exposure of human cells to this chemical. Currently, it is not known whether results from cells in vitro can be extrapolated to human health consequences of chemical exposure.

Key Words: DNA microarray analysis • gene expression • health effects induced by agricultural chemicals • organophosphate insecticides • real time PCR

Human & Experimental Toxicology, Vol. 25, No. 5, 225-233 (2006)
DOI: 10.1191/0960327106ht622oa


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