Cadmium (Cd) is a toxic and carcinogenic
metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and
cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human
hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several
metallothioneins. Downregulated genes included the
monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J
protein. Genes downregulated following chronic exposure included the transcriptional regulator
early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and
urological diseases/
cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in
carcinogenesis. In addition to gene expression changes, HepG2 cells treated with
cadmium for 24h indicated a reduction in global levels of
histone methylation and acetylation that persisted 72 h post-treatment.