title: Evidence of in vivo peroxynitrite formation in patients with colorectal carcinoma, higher plasma nitrate/nitrite levels, and lower protection against oxygen free radicals.
abstract: Endogenously formed nitrogen and oxygen free radicals are believed to be involved in human cancer etiology. Plasma nitrate/nitrite originates from endogenous nitric oxide production in fasting humans, decrease in superoxide scavenger activity (SSA), and free sulfhydryl groups (SH) reflects the amount of superoxide anion generated, and nitrotyrosine is believed to be formed by the interaction of tyrosine and peroxynitrite in vivo. The aim of the current study was to measure plasma nitrate/ nitrite, SSA, and SH in 69 patients (mean age +/- standard deviation, 66 +/- 11 years) with colorectal carcinoma. Nitrotyrosine was measured from both the plasma and tumor tissues in 32 patients. All patients had adenocarcinoma of the colon or rectum. Twenty-five patients were classified as stage B according to Dukes classification as modified by Astler-Coller, 13 were classified as stage C, and 31 patients were classified as stage D. To determine whether the changes are specific for colorectal cancer, 20 patients with active inflammatory bowel disease (IBD; mean age, 52 +/- 18 years) and 30 healthy volunteers, who served as control subjects (mean age, 48 +/- 11 years), were studied. Plasma nitrate/nitrite was measured by the modified Griess method, SSA was measured by an electron/spin resonance spin trapping method, free SH was measured by Ellman's method, and the presence of nitrotyrosine in the plasma and tumor tissue was detected by high performance liquid chromatography (HPLC) using C- 18-derivatized silica (5 microm) column (C18S, Crestpaque, New York, NY, USA) and at a wavelength of 274 nm. Patients with colorectal carcinoma and with active IBD had a significantly higher plasma nitrate/ nitrite level (51.2 +/- 26.2 microm and 56.0 +/- 14.6 microm versus. 29.6 +/- 6.3 microm; p < 0.01), and a lower SSA level (39 +/- 11.5 U/g protein and 52.0 +/- 18.9 U/g protein versus. 88 +/- 25.1 U/g protein; p < 0.05) and SH level (7.7 +/- 3.89 microm protein and 6.4
authors.affiliation: 2nd Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Szaleczky
authors.forename: L
authors.initials: L
authors.lastname: Prónai
authors.forename: H
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Z
authors.initials: Z
authors.lastname: Tulassay
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D016877:Oxidants / Q000378:metabolism*; D017382:Reactive Oxygen Species
chemical_list: D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D017382:Reactive Oxygen Species; C039642:peroxynitric acid