Clinical Medicine Reviews in Oncology

Arsenic is present at low concentrations in nearly all aquatic environments and exposures through drinking water have been reported in many countries. Chronic exposure to high-levels of arsenic through drinking water is associated with skin, lung, kidney, liver and bladder cancer. Current evidence suggests that the liver is an important target of arsenic toxicity. cDNA microarray technology was used as a sensitive low-level monitor of the impact of arsenic in an in vitro model of exposure. In this study we examined the gene expression alteration in human hepatoma (HepG2) cells following exposure to low-levels of arsenic. HepG2 cells were exposed for 6 or 24 hours to sodium arsenite concentrations of either 0.1 μM or 10 μM. Arsenic at levels ranging from less than 0.1 μM to greater than 10 μM have been reported in drinking water sources from various parts of the world. Total RNA from treated and control cells were isolated, reverse transcribed and reciprocal labelled with Cy3 and Cy5 dyes and hybridized to a human cDNA microarray. The hybridized microarray chips were scanned, quantified and analyzed to identify genes affected by sodium arsenite exposure based on a two-fold increase or decrease in gene expression and reproducibility (affected in three or more treatments). Following filtering, normalization and hierarchical clustering initial data indicate that at least twenty-two genes were found to be commonly expressed in the treatments of sodium arsenite tested. The affected genes indicate that HepG2 cells respond to low-level sodium arsenite exposures and the cellular response is associated with alterations in expression of several genes. The affected genes were characterized as structural, immune response, regulatory and cell cycle genes. Identification of these target genes may help to highlight potential new pathways in which to further probe the effects of low-level arsenite exposures.