Wound healing is a complex process involving a number of related genes and receptors. Using cDNA microarrays, we explored the global gene expression profile of phenytoin (20 mug/ml) induced changes to human dermal fibroblasts. Microarray data analysis revealed similar to1500 genes were differentially expressed by 2.5-fold. At 3, 6, 12, and 24h, the transcripts of the major growth factors involved in wound healing and their receptors were increased. This was further confirmed by RT-PCR. Genes encoding other proteins with roles in signal transduction (NFkappaB), extracellular matrix (MMP1) including type I collagen, fibronectin, and laminin were strongly induced at 6h and onwards. Genes involved in cell cycle regulation (CCND1 and CDKN1A) were down-regulated consistent with our finding that phenytom per se did not have cell proliferation activity. Notably, phenytoin accelerates the autocrine and paracrine activity of growth factors by up-regulating the related receptors. (C) 2003 Elsevier Inc. All rights reserved.