Gene expression patterns in human liver cells exposed to tetrachloroethylene and it's metabolite using microarray analysis.
Environ Mol Mutagen 2003 May; 41(3):182
Occupational exposure to tetrachloroethylene (TCE) occurs through inhalation, skin contact or ingestion during its use in dry cleaning and degreasing. Tetrachloroacetic acid (TCA), a major end metabolite of TCE, has been reported in human blood and urine after exposure to TCE. In our laboratory, studies have been conducted to determine changes in gene expression patterns in cultured human cells exposed to TCE and TCA. Exponentially growing normal human liver cells were treated with 200 and 400 uM of TCE or TCA for 12h. Total RNA was used for the preparation of double stranded cDNA. Biotin labeled cRNA transcripts were synthesized, fragmented and hybridized to HuGeneFL GeneChip probe arrays representing more than 6800 human genes and expressed sequence tags. The arrays were stained with streptavidin-phycoerythrin and biotinylated anti- streptavidin antibodies. The differential gene expression data analysis was performed using GeneChip 4.0 software. Altered gene expression was observed in at least 35 genes with a 2 fold or more change in both TCE and TCA-exposed group. Significantly higher expression was observed in tumor necrosis factor receptor in the TCA treatment group compared to the parent compound - TCE. Similarly, expression of heat shock protein 70 increased 8.8 fold in TCA treatment group compared to TCE treatment which had 2.7 fold increase. However, certain genes such as elongation factor1 delta, initiation factor 2B-3, m- phase phosphoprotein had a marginal increase in response to both TCE and TCA compared to control group. These results indicate that metabolite compound preferentially affects certain set of genes. Whether difference in the expression patterns of these genes is associated with difference in carcinogenic potential of TCE and/or TCA needs to be elucidated.
Inhalants; Skin; Skin-absorption; Dry-cleaning-solvents; Dry-cleaning-industry; Genes; Genetic-factors; Liver-cells; Metabolites; Carcinogens
National Institute for Occupational Safety and Health,Toxicology and Molecular Biology Branch, 1095 Willowdale Road, Morgantown, WV 26505
Conference/Symposia Proceedings; Abstract
Research Tools and Approaches: Cancer Research Methods
Environmental and Molecular Mutagenesis