Abstract
Arsenic is ubiquitous in the world as it is widely used as termiticide, wood preservatives and etc. Chronic ingestion of food and water contaminated with arsenic can cause several disorders including skin and lung cancer.
To assess a chronic toxicity of low-level arsenic in the environment, we need to discover a sensitive biomarker for detecting a low concentration of arsenic. We applied a new novel sensitive comprehensive gene expression analysis method named HiCEP to normal human lung fibroblasts (HFLIII cells) and searched over 10,940 transcripts which responded to 1 microM sodium arsenite (NaAsO2). We identified the transcript mostly up-regulated in response to 1 microM NaAsO2 as heme oxygenase 1 (HMOX1). In order to determine the optimal incubation time required for the maximum expression of HMOX1 induced by NaAsO2, we measured HMOX1 mRNA expression level in HFLIII cells exposed to 1-10 microM NaAsO2 for 2, 4, 8, 12, or 24 hours by qPCR. It was acertained that HMOX1 expression reached to the maximum level after 4 hours' treatment with arsenite. As 1 microM NaAsO2 hardly affect the cell viability, we examined the effect of less than 1 microM NaAsO2 on the expression of HMOX1. HMOX1 expression reached to the maximum level after 2-4 hours' treatment with 0.3-1 microM NaAsO2, and was significantly enhanced in HFLIII cells treated with the low concentration of arsenite compared with sham treated cells. These results indicate that HMOX1 is a good biomarker for the detection of a low level of arsenic in the environment.
Next, we examined whether or not HMOX1 can be a biomarker for the assessment of the effect of ionizing radiation. X-ray irradiation didn't significantly affect the HMOX1 expression.
Taken together, these results demonstrate HiCEP could be a useful method to find biomarkers for the assessment of the effect of toxicants including arsenic in the environment.
