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.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Mankame T,Hokanson R,Fudge R,Chowdhary R,Busbee Ddoi
10.1191/0960327106ht593oasubject
Has Abstractpub_date
2006-02-01 00:00:00pages
57-65issue
2eissn
0960-3271issn
1477-0903journal_volume
25pub_type
杂志文章abstract::1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappr...
journal_title:Human & experimental toxicology
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