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APPLICATION OF CDNA MICROARRAY TO THE STUDY OF ARSENIC TOXICOLOGY AND CARCINOGENESIS
Citation:
Liu, J., H. Chen, T. Lu, M. Waalkes, AND J. L. Mumford. APPLICATION OF CDNA MICROARRAY TO THE STUDY OF ARSENIC TOXICOLOGY AND CARCINOGENESIS. Presented at Society for Environmental Geochemistry and Health (SEGH), 4th International Conference on Arsenic Exposure and Health Effects, San Diego, CA, June 18-21, 2000.
Description:
Arsenic (As) is a common environmental toxicant and known human carcinogen. Epidemiological studies link As exposure to various disorders and cancers. However, the molecular mechanisms for As toxicity and carcinogenicity are not completely known. The cDNA microarray, a high-throughput analysis of gene expression, was used to profile the genetic events associated with inorganic As exposure in the liver. In mice, following acute As+3 and As+5 exposure, expression of many oxidative stress-related genes (such as heme oxygenase 1) were markedly increased, along with the upregulation of DNA damage-inducible genes, and the downregulation of genes encoding for drug metabolizing enzymes. In murine liver epithelial cells chronically exposed to As+3, the upregulation of many oncogenes (such as c-myc, c-fos, c-jun and c-met) was associated with As-induced malignant transformation. In liver biopsy samples from As-exposed humans in Guizhou, China, expression of E2F, c-met, and superoxide dismutase was increased, while many apoptosis-related genes, such as caspases, were downregulated. In summary, the microarray analysis revealed important aberrant gene expression patterns occurring with As exposure in humans and rodents. These initial gene array studies could be critical in future studies designed to more fully elucidate the molecular mechanisms of As toxicity. [This abstract does not reflect official US EPA policy.]
CORRESPONDING AUTHORS: Jie Liu, Ph.D., and Michael P. Waalkes, Ph.D., Inorganic Carcinogenesis Section, NCI at NIEHS, Mail Drop F0-09, 111 Alexander Drive, Research Triangle