Biomarkers of Exposure to Toxic Substances. Volume 2: Genomics: Unique Patterns of Differential Gene Expression and Pathway Perturbation Resulting from Exposure to Nephrotoxins with Regional Specific Toxicity

摘要

Toxicity commonly occurs after exposure to a variety of chemicals agents. Changes in gene expression are among the most sensitive indicators of chemical exposure. Toxicogenomics, which is based on DNA microarray technology, is the study of the cellular response to chemical insults at the transcriptomic level by simultaneous measurement of the expression levels of virtually all expressed genes. Therefore, this technology is a useful technique for studying the molecular mechanism of chemical-induced toxicity. In this study, DNA microarray technology was used in combination with advanced bioinformatic techniques to evalauate its utility in assessing gene expression changes and subsequently the mechanism of renal injury following exposure to nephrotoxins selected for their regional specific toxicity. Four chemicals, hippuric acid, D- serine, puromycin and amphotericin B, which induce glomerular and tubulointerstitial damage, necrosis of the pars recta region of the proximal tubules, glomerular injury, and distal tubular damage, respectively, were used in this study. The effects of exposure to these chemicals on renal differential gene expression and the biological implication of these gene expression changes were investigated.