Toxicogenomic and signaling pathway analysis of low-dose exposure to cadmium chloride in rat liver

Humans are chronically exposed to low doses of the environmental pollutant Cadmium (Cd). Despite the low doses of exposure, several studies have reported that Cd is carcinogenic and affects cellular functions in humans. However, little is known about its toxicity mechanisms. To further understand cadmium's biological effects and toxicity mechanisms, we employed DNA microarray techniques and Pathway Studio software to study altered gene expressions and pathway analyses for several genes in rat liver exposed to cadmium chloride (low dose of 0.25 or 2.5 mg/kg/day). A total of 530 genes exhibited differentially altered gene expression, and of those, 103 genes were commonly expressed in both Cd-treated groups. Of the 103 genes, 49 were commonly up-regulated genes, whereas, 54 were commonly down-regulated genes. We visualized signaling pathways of the commonly expressed genes and selected cell process and disease related pathways with high gene connections. In the pathways, several genes, including EBAG9, ITGB2, HIPK2, and SLK, were predicted as key players. These findings suggest that low-dose Cd exposure might induce various toxic processes including apoptosis, regulation of cell growth, neoplasm, and cancer. Moreover, the identified genes could be used as Cd-specific potential biomarkers.