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Altered gene expression in human cells treated with the insecticide diazinon: correlation with decreased DNA excision repair capacity.

Authors
Mankame-T; Hokanson-R; Fudge-R; Chowdhary-R; Busbee-D
Source
Hum Exp Toxicol 2006 Feb; 25(2):57-65
NIOSHTIC No.
20029772
Abstract
Many industrial and agricultural chemicals have steroid hormone agonist or antagonist activities and disrupt hormone-regulated gene expression. The widely-used agricultural insecticide, diazinon, was evaluated using MCF-7 cells - a breast cancer-derived, estrogen-dependent, human cell line - to examine the capacity of this chemical to alter steroid hormone-regulated gene expression. MCF-7 cells were treated with 30, 50, or 67 ppm of diazinon, and gene expression in treated cells was measured as mRNA levels in the cells compared to mRNA levels in untreated or estrogen-treated cells. DNA microarray analysis showed significant up- or down-regulation of a number of genes in treated cells compared to untreated cells. Of the 600 human genes on the chip utilized, specific genes with related functions were selected for additional consideration. Real time quantitative PCR (qrtPCR) completed to corroborate mRNA levels as a measure of specific gene expression, confirmed results obtained from analysis of the micro-array data. The data show that ERCC5, encoding Xeroderma pigmentosum protein G (XPG), essential for DNA excision repair, and ribonucleotide reductase subunit M1 (RNRM1), encoding a gene necessary for providing the nucleotides needed for DNA repair, were down-regulated in cells treated with diazinon. These studies were designed to provide base-line data on the gene expression-altering capacity of a specific agricultural chemical, diazinon, and allow assessment of some of the potentially deleterious effects associated with exposure of human cells to diazinon.
Keywords
Genes; Insecticides; DNA-damage; Agricultural-chemicals; Organo-phosphorus-pesticides; Pesticides-and-agricultural-chemicals; Pesticides
CODEN
HETOEA
CAS No.
333-41-5
Publication Date
20060201
Document Type
Journal Article
Funding Type
Cooperative Agreement
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U50-OH-007541
Issue of Publication
2
ISSN
0960-3271
Source Name
Human and Experimental Toxicology
State
TX
Performing Organization
University of Texas Health Center at Tyler
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