Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters.

Microsatellite polymorphism in the promoter region of the heme oxygenase-1 (HO-1) gene was analyzed jointly with that of the inducible nitric oxide synthase (iNOS) gene among Japanese subjects (control and gastric cancer patients). A higher promoter activity genotype of the HO-1 gene was associated with increased risk for gastric cancer in women. Gastric cancer risk was notably increased in subjects carrying a higher promoter activity genotype for both HO-1 and iNOS compared to those with a lower promoter activity genotype for both genes.

Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerates sarcoma development in Trp53+/- mice.

Chronic inflammation is a recognized risk factor for human cancer at various sites because of persistent oxidative and nitrative tissue damage. Trp53+/- mice show the predisposition to tumor development, such as sarcomas and lymphomas, compared with Trp53+/+ mice. We investigated the effects of chronic inflammation, especially oxidative and nitrative stress, induced by subcutaneous implantation of a plastic plate (10 x 5 x 1 mm) as a foreign body on tumorigenesis in Trp53+/- and Trp53+/+ mice.

Increased risk of intestinal type of gastric adenocarcinoma in Japanese women associated with long forms of CCTTT pentanucleotide repeat in the inducible nitric oxide synthase promoter.

Tandem repeat number polymorphism of a CCTTT pentanucleotide in the promoter region of the inducible nitric oxide synthase gene (iNOS) and a polymorphism of the interleukin-1beta (IL-1B) promoter at position -31 were analyzed in DNA samples from 181 Japanese control subjects and 158 gastric cancer patients, including 96 intestinal type and 62 diffuse type. An association between the intestinal type of gastric adenocarcinoma and higher promoter activity of the iNOS gene was found in women, especially those having higher promoter activity of the IL-1B gene and without a history of smoking. Our results imply that chronic inflammation caused by excess nitric oxide generated by iNOS contributes to Helicobacter pylori-induced gastric cancer.

Nitration and nitrosation of N-acetyl-L-tryptophan and tryptophan residues in proteins by various reactive nitrogen species.

Proteins are targets of reactive nitrogen species such as peroxynitrite and nitrogen dioxide. Among the various amino acids in proteins, tryptophan residues are especially susceptible to attack by reactive nitrogen species. We carried out experiments on the reactions of peroxynitrite and other reactive nitrogen species with N-acetyl-L-tryptophan under various conditions.