Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients

Abstract

Saliva and 24-h urine samples were collected from male Schistosomiasis (bilharzia) patients with S. haematobium infection and possible concurrent S. mansoni infection without diagnosed bladder cancer (n = 27), bilharzia patients with diagnosed bladder cancer (n = 23) as well as a comparative control group (n = 27) of healthy Egyptian volunteers with no current bilharzia infection and/or bacterial urinary tract infections from the Nile Delta area of Egypt. Saliva samples were analysed for the presence of nitrate and nitrite; urine samples were analysed for the presence of nitrate, nitrite, volatile and non-volatile N-nitroso compounds. Bilharzia patients prior to, and after, diagnosed bladder cancer regularly excreted free nitrite as well as volatile nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopiperidine and N-nitrosopyrrolidine) in addition to which elevated concentrations of non-volatile N-nitrosamino acids (N-nitrosoproline, N-nitrososarcosine, N-nitrosothiazolidine-4-carboxylic acid and its 2-methyl derivative) were also present. Total urinary excretion of volatile N-nitroso compounds (0.32 +/- 0.64 micrograms/day; mean +/- SD) and non-volatile N-nitroso compounds (31.20 +/- 22.07 micrograms/day) was observed in the Egyptian control group. Significantly higher concentrations were found in bilharzia patients: 3.47 +/- 6.42 (P less than 0.05) and 62.91 +/- 21.96 (P less than 0.05); as well as in bilharzia patients with diagnosed bladder cancer: 1.71 +/- 1.96 (P less than 0.02) and 44.94 +/- 7.31 respectively. Free nitrite was found in the urine of two volunteers in the Egyptian control group (1.7 and 3.0 micrograms/day), urinary nitrite was significantly increased in bilharzia patients (5.18 +/- 9.11 micrograms/day, P less than 0.02) and in bladder cancer patients (1.75 +/- 2.81 micrograms/day, P less than 0.05). Nitrate concentrations were elevated from 139.3 +/- 82.2 in the control group to 143.6 +/- 136.3 and 175 +/- 190 in the bilharzia and bladder cancer groups respectively. These results indicate that significant in vivo formation of nitrite and volatile N-nitroso compounds occurs in the urinary bladder of bilharzia patients and this may be an oetiological factor in the induction of bilharzial bladder cancer associated with S. haematobium infection.

Chronic bacterial and parasitic infections and cancer: a review

“…It should be noted that nitrate-reducing bacteria and increased levels of urinary and saliva Nnitrosamines levels were observed to be highest in patients with schistosomal infections compared to those in healthy controls [59,65,91,92]. This observation lends credence to the notion that nitrosamines play an essential role in schistosomiasis-associated bladder cancer [69,73,93].…”

DNA damage and mutation in human cells exposed to nitric oxide in vitro.

“…Studies on one human subject with chronic active hepatitis resulting from hepatitis B virus infection also demonstrate greatly elevated urinary nitrate output (C. Leaf and S.R.T., unpublished results). Elevated urinary nitrate has also been found in humans infected with liver flukes at elevated risk for cholangiocarcinoma (42) and in populations infected with Schistosomiasis mansoni (43). Since the nature of mutations in key genes (protooncogenes and/or tumor suppressor genes) in the last two tumor sites is unknown, these might be important experiments to test the generality of our hypothesis that nitrosative deamination is an important mechanism of mutagenesis leading to some human cancers.…”

Nrf2 Is Essential for the Chemopreventive Efficacy of Oltipraz against Urinary Bladder Carcinogenesis

“…Currently, cigarette smoking is considered a major risk factor for the development of bladder cancer in industrialized countries (1). Similarly, N-nitroso compounds (NOCs) have been proposed as etiologic agents of bladder cancer associated with schistosomiasis (3). NOCs also are thought to play roles in the carcinogenesis of the stomach, esophagus, and pharynx in humans (4).…”