Identification of differentially expressed genes in the livers of chronically i-As-treated hamsters

Inorganic arsenic (i-As) is a human carcinogen causing skin, lung, urinary bladder, liver and kidney tumors. Chronic exposure to this naturally occurring contaminant, mainly via drinking water, is a significant worldwide environmental health concern. To explore the molecular mechanisms of arsenic hepatic injury, a differential display polymerase chain reaction (DD-PCR) screening was undertaken to identify genes with distinct expression patterns between the liver of low i-As-exposed and control animals. Golden Syrian hamsters (5–6 weeks of age) received drinking water containing 15 mg i-As/L as sodium arsenite, or unaltered water for 18 weeks. The in vivo MN test was carried out, and the frequency of micronucleated reticulocytes (MN-RETs) was scored as a measure of exposure and As-related genotoxic/carcinogenic risk. A total of 68 differentially expressed bands were identified in our initial screen, 41 of which could be assigned to specific genes. Differential level of expression of a selected number of genes was verified using real-time RT-PCR with gene-specific primers. Arsenic-altered gene expression included genes related to stress response, cellular metabolism, cell cycle regulation, telomere maintenance, cell–cell communication and signal transduction. Significant differences of MN-RET were found between treated (8.70 ± 0.02 MN/1000 RETs) and control (2.5 ± 0.70 MN/1000 RETs) groups (P < 0.001), demonstrating both the exposure and the i-As genotoxic/carcinogenic risk. Overall, this paper reveals some possible networks involved in hepatic arsenic-related genotoxicity, carcinogenesis and diabetogenesis. Additional studies to explore further the potential implications of each candidate gene are of especial interest. The present work opens the door to new prospects for the study of i-As mechanisms taking place in the liver under chronic settings.

► Hamsters were chronically exposed to low doses of inorganic arsenic.
► Genotoxic/carcinogenic effects were detected as increased MN-reticulocytes.
► 48 differentially expressed genes in livers were detected by DD-PCR.
► Altered genes are related to a variety of molecular and cellular mechanisms.
► Links involving genotoxicity, carcinogenicity and diabetogenesis are suggested.