Constitutive upregulation and a higher degree of induction of drug metabolism and disposition-related genes were found in a three-dimensional HepG2 Culture. The upregulated genes are believed to be regulated by different regulatory factors. Global gene expression analysis using the Affymetrix GeneChip indicated that altered expression of microtubule-related genes may change the expressed levels of drug metabolizing and disposition genes. Stabilization of microtubule molecules with docetaxel, a tubulin-stabilizing agent. in the two-dimensional culture showed gene expression patterns similar to those found in the three-dimensional culture, indicating that the Culture environment affects drug metabolism functions in HepG2 cells. (C) 2008 Elsevier Inc. All rights reserved.