Tumor necrosis factor-alpha (TNF-alpha) inducing protein (Tip alpha) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-alpha and chemokine genes and activation of nuclear factor-kappa B. Since Tip alpha enters gastric cancer cells, the Tip alpha binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip alpha was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip alpha and DNA, revealed that the affinity of Tip alpha for (dGdC)10 is 2400 times stronger than that of del-Tip alpha, an inactive Tip alpha. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tip alpha. And the DNA-binding activity of Tip alpha was first demonstrated with a molecule secreted from H. pylori. (c) 2007 Elsevier Inc. All rights reserved.