Abstract
Tetrachloroethylene (TCE), is an industrial solvent widely used in dry cleaning, textile-processing, degreasing fabricated metal parts and paint stripping. Occupational exposure to TCE can occur through inhalation, skin contact or ingestion during its use in dry cleaning and degreasing. Although there IS limited evidence in humans for carcinogenicity of TCE, it is classified as a probable carcinogen to humans by International Agency for Research on Cancer. In this study, we have investigated TCE exposure and global gene expression pattern in normal human liver cells using microarray analysis. Exponentially growing cells were exposed to a final concentration of 200 and 400 uM of TCE for 12 h. Total RNA was used for the preparation of double stranded cDNA. Biotin labeled cRNA transcript was synthesized using cDNA, fragmented and hybridized to HuGeneFL GeneChip probe arrays representing more than 6800 human genes and expressed sequence tags. The arrays were stained with streptavidinphycoerythrin and biotinylated anti-streptavidin antibodies. The differential gene expression data analysis was performed using GeneChip(r) 4.0 software. The 3'/5' cRNA transcript ratios for both GAPDH and a-actin were found to be consistent between control and treatment groups over a period of 12 h exposure. Altered gene expression pattems were observed in 194 RNA transcripts with at least a 2 fold change. Alterations in expression of some of the genes include XRCC4, Rad51, Has2, metalloproteinase, MDM2 gene, TNF receptor, Ra1, heat shock protein 70, TNF-receptor-1 associated protein (TRADD). The results indicate that TCE induces changes in expression of certain important cell cycle regulation genes. Whether these genes are directly involved in the process of TCE-induced carcinogenesis needs to be elucidated.
