Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of the most abundant. We examined the effect of DADS on gene expression in rat liver. By suppressive subtractive hybridization, we identified the heavy (H)-ferritin gene as a DADS-stimulated gene in the rat liver epithelial (REL) cells. DADS stimulation of H- and L (light)-ferritin mRNA was analyzed in REL cells and in rat liver. Incubation of the REL cells in 10 micro mol/L DADS for 4 h increased H-ferritin 1.9 +/- 0.2-fold, n = 3) and light(L)-ferritin mRNA 1.5 +/- 0.2-fold, n = 3). Stimulation did not occur in the presence of an inhibitor of transcription, actinomycin D. Stimulation of ferritin at the RNA and protein levels was also found in rats administered a DADS-enriched oil solution intragastrically. There was a 3 +/- 1.1-fold increase in H- and 3 +/- 0.14-fold increase for L-ferritin mRNA 24 h after the end of the infusion in the presence of DADS, (n = 3). The expression of the transferrin receptor, an iron transporter, was also enhanced by DADS in rat liver. In conclusion, our data suggest that DADS could modify iron homeostasis through the modulation of ferritin and transferrin receptor gene expression.