The liver has the unique ability to regenerate even in adulthood. While mature hepatocytes can proliferate by themselves, stem cells also play a critical role in liver regeneration and oval cells are considered to be the progeny of activated hepatic stem cells. We herein investigated the gene expression profiles in the conditions inducing oval cells, using microarray analysis. Two approaches were used to induce oval cells. In the first, animals were treated with a combination of an N-2-acetylaminofluorene (AAF)-containing diet and partial hepatectomy (PHx). In the second, animals were supplied with chow containing a 1:1 mixture of choline-deficient and normal diets, as well as 0.075% ethionine in drinking water. Using in-house cDNA microarrays consisting of 2304 cDNA clones from the mouse liver, 69 and 89 genes, respectively, were found to be up-regulated in these two models. Six genes, i.e., those for insulin-like growth factor binding protein-1, CYP4a14, carnitine octanoyltransferase, osteopontin, and two expressed sequence tags (ESTs) were up-regulated in these models but not in ordinary model with PHx alone. They might be specifically activated in the induction of oval cells, and help to clarify the nature of stem cell stimulation that occurs during liver regeneration. (C) 2004 Elsevier Inc. All rights reserved.