Application of cDNA Microarray Technology to In Vitro Toxicology and the Selection of Genes for a Real-Time RT-PCR-Based Screen for Oxidative Stress in Hep-G2 Cells

Large-scale analysis of gene expression using cDNA microarrays promises the rapid detection of the mode of toxicity for drugs and other chemicals. cDNA microarrays were used to examine chemically induced alterations of gene expression in HepG2 cells exposed to a diverse group of toxicants at an equitoxic exposure concentration. The treatments were ouabain (43 μM), lauryl sulfate (260 μ M), dimethylsulfoxide (1.28 M), cycloheximide (62.5 μM), tolbutamide (12.8 mM), sodium fluoride (3 mM), diethyl maleate (1.25 mM), buthionine sulfoximine (30 mM), potassium bromate (2.5 mM), sodium selenite (30 μM), alloxan (130 mM), adriamycin (40 μM), hydrogen peroxide (4 mM), and heat stress (45•C × 30 minutes). Patterns of gene expression were correlated with morphologic and biochemical indicators of toxicity. Gene expression responses were characteristically different for each treatment. Patterns of expression were consistent with cell cycle arrest, DNA damage, diminished protein synthesis, and oxidative stress. Based ...