Vitamin E has been described in the literature as a regulator of gene expression. The gene-regulatory activity of vitamin E with regard to genes encoding cytochrome P450 (CYP) enzymes, which play a pivotal role both in the metabolism of xenobiotics and vitamin E, has not been conclusively characterised. The objective of the current study was, therefore, to elucidate the short- and long-term effects of natural and synthetic vitamin E on CYP gene expression using Affymetrix GeneChip (R) technology. To this end, HepG2 cells were incubated with 0, 10, 30, 80 and 300 uM RRR-a-tocopheryl acetate (natural vitamin E) or all rac-a-tocopheryl acetate (synthetic vitamin E) for 7 days and the mRNA of CYP genes was quantified. The expression of only one (CYP20A1) of 14 CYP genes with detectable mRNA levels was dose-dependently up-regulated. No differences in gene-regulatory activity were observed between RRR- and all rac-a-tocopheryl acetate. To study the role of vitamin E in CYP gene expression in vivo, Fisher 344