Abstract

Endogenously formed nitroso-compounds and nitrite-derived mutagens are believed to be involved in human cancer etiology. These nitroso-compounds can be formed from nitric oxide by macrophages and neutrophils by means of the inducible nitric oxide synthase. Increased nitric oxide synthase expression has been reported in patients with colon carcinoma. Since endogenous nitric oxide synthesis is responsible for the majority of plasma nitrate/nitrite levels, we investigated plasma nitrate/nitrite levels in colorectal carcinoma patients (mean age 66±2.2 y.). Thirteen healthy volunteers comprised the control group (mean age 28±1.9 y.). All patients had been diagnosed with adenocarcinoma (11 rectum, 12 colon, 2 both the rectum and colon), mostly within one year of the study and 50% of patients underwent surgery and/or chemotherapy within one month of the study.Thirteen patients were classified as stage B or C and 15 patients had stage D, according to the Dukes classification modified by Astler-Coller and Turnbull. Since cardiac failure and nitric oxide releasing drugs (such as nitroglycerine) may increase plasma nitrate/nitrite levels, patients had also been divided according to their medication and cardiac condition. Considering the total number of patients, cancer patients demonstrated no statistically different plasma nitrate/nitrite levels, in comparison with healthy controls. However, patients with a tumor diagnosed more than a half year prior to the study, had significantly higher nitrate/nitrite levels compared to the group of patients diagnosed within six months of the study (p=0.03). Patients who underwent chemotherapy within one month of the study, also demonstrated significantly higher nitrate/nitrite levels compared to the group of patients who had no chemotherapy during the past four weeks (p=0.04). Plasma nitrate/nitrite levels were higher in patients with no prior surgery. There was no statistically significant difference in patients when assessing the location of the tumor, presence or absence of distal metastasis, medication used or cardiac condition.Actual plasma nitrate/nitrite levels are indirect measures of malignant diseases. They do not reflect earlier staging, location or severity of the colorectal carcinoma but seem to positively correlate with the duration of the disease. Chemotherapy increases plasma nitrate/nitrite levels by enhancing cell degradation.

Keywords: peroxynitrite, Nitric Oxide, colorectal cancer