Discriminating two classes of toxicants through expression analysis of HepG2 cells with DNA arrays

Microarray technology provides a rapid and cost-effective method to associate specific cellular responses with unique gene expression patterns. If characteristic expression patterns of a small number of genes could be associated with drug toxicity, this association may be used for toxicity prediction, and thereby to reduce the need for traditional toxicity testing. To test this hypothesis, we have designed an array composed of 92 known human genes of toxicological interest (including seven housekeeping genes) and eight bacterial controls. HepG2 cells were treated with either ethanol or one of two quinone containing anticancer drugs, mitomycin C or doxorubicin. RNA was isolated from treated and untreated cells, differentially labeled with fluorescent dyes, and then hybridized to the array. Our results show that the expression patterns induced by ethanol and the anticancer drugs are different. Both of the anticancer drugs, but not ethanol had a differential effect on the regulation of several genes, including CYP4F2/3, CYP3A3, TNFRSF6 and CHES1, demonstrating that the two drugs might function through a similar mechanism, which differs from that of ethanol. These results suggest that microarray-based expression analysis may offer a rapid and efficient means for assessing drug toxicity. (C) 2002 Elsevier Science Ltd. All rights reserved.