An Evaluation of the Dna Array for Use in Toxicological Studies

Abstract

Important issues facing toxicologists when assessing the risks of chemical exposure include incomplete understanding of the mechanisms of toxicity and the need to predict the outcome of exposure to new compounds. New technologies capable of providing vast amounts of information hold promise for both mechanistic understanding and outcome prediction. High-density nucleic acid arrays, or DNA arrays, are one such technology. Before being used as a predictive or mechanistic tool, it is critical that DNA array technology be evaluated in a toxicological setting.

In the present study, a series of experiments was conducted to determine the reliability of the DNA array. An acceptable degree of reproducibility was observed in replicate and interanimal comparisons. These data provide criteria to define significance for gene expression ratios generated in control and experimental conditions. Subsequently, ex vivo experiments were conducted to evaluate the utility of the DNA array in predicting toxicological endpoints. Results of these experiments correlated well with eventual biochemical lesions. Furthermore, changes that were observed in regulated genes capitulated those reported in the literature. For example, differential gene expression was identified in the auricular lymph nodes of mice exposed to a known dermal sensitizer, 1-chloro-2,4-dinitrobenzene, and in the livers of rats dosed with the hepatotoxicant furan. Overall, the DNA array proved to be a reliable tool for detecting simultaneous gene expression.

Key Words:

• DNA array
• local lymph node assay
• mouse
• rat
• toxicogenomics