Identification of genes induced by carbamazepine in human bronchial epithelial BEAS-2B cells

Abstract

Some drugs are limited in their clinical application due to their propensity for inducing adverse side effects. We examined some clinical chemotherapeutic agents that have pulmonary toxic effects. Carbamazepine (CBZ) is an antiepileptic agent and its long-term use is associated with interstitial pneumonia, pulmonary fibrosis, and pulmonary infiltration with eosinophilia. CBZ is persistent in the environment and is frequently detected in water systems. A new technique in toxicity screening, “toxicogenomic technology”, represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process and their potential effects on the environment. To this end, we have examined gene expression profiles in BEAS-2B cells (a human bronchial epithelial cell line) following exposure to CBZ, which induced pulmonary toxicity, by using a human oligonucleotide chip. We identified 518 up- and 496 down-regulated genes whose expression had changed by more than 1.5-fold (p<0.01) following CBZ exposure. Gene Ontology (GO) analysis showed elevation in the expression of genes involved in several key biological processes related to pulmonary toxicity, such as cholesterol metabolism, cell proliferation, and cell cycle regulation. In conclusion, the present study indicates that CBZ exerts its toxicity by modulating mRNA expression in BEAS-2B cells. We suggest that genes expressed by CBZ might serve as a molecular signature, which could be used more widely when implemented in combination with more traditional techniques, for the assessment and prediction of toxicity following CBZ-exposure.