Determination of cytosolic citrulline and nitrate as indicators of nitric oxide in bladder cancer: possible association with basic fibroblast growth factor

Abstract

Background: Nitric Oxide (NO) and nitrosamines have been implicated in bladder carcinogenesis. Apart from its implication in carcinogenesis, NO contributes to the regulation of tumor angiogenesis via angiogenic peptides exemplified by basic fibroblast growth factor (bFGF). Objectives and methods: In order to examine NO pattern in normal, schistosomal, and malignant bladder cytosols, we have used a combined approach by measuring nitrate and the amino acid citrulline. The results were correlated to bFGF, which were measured in bladder cytosols by an EIA method. Results: Comparison between normal, schistosomal, and malignant bladder groups showed that patients with schistosomiasis and bladder cancer had significantly higher cytosolic nitrate, citrulline, and bFGF levels. There were no apparent correlations between these investigated parameters and tumor histologic features. The level of citrulline was strongly correlated to nitrate level and both were correlated to bFGF level in bladder cancer and schistosomiasis groups. Conclusions: Our findings indicate that NO and bFGF were significantly elevated in schistosomiasis and bladder cancer compared to normal bladders. Moreover, the consistent association of NO with bFGF found in the present work, support the hypothesis that the angiogenic peptide bFGF may be modulated by NO and suggest a useful target in antiangiogenic therapy in bladder cancer.