Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients

Abstract

The present study presents, for the first time, the amounts of nitrate, nitrite and volatile N-nitroso compounds in saliva and urine samples of Schistosoma haematobium and Schistosoma mansoni infected patients. Mid-morning saliva and 24 h urine samples were collected from male patients infected with S.haematobium (n = 129 saliva and 79 urine samples) and S.mansoni (n = 64 saliva and 65 urine samples) and in a comparative control group of healthy individuals (n = 27) from the Nile Delta region of Egypt. Saliva samples were analyzed for the presence of nitrate and nitrite; while urine samples were analyzed for the presence of nitrate, nitrite and volatile N-nitroso compounds. In the control group, N-nitroso-dimethylamine (NDMA) was detected at concentrations (mean +/- SD) of 0.27 +/- 0.47 microgram/day. N-Nitrosopiperidine (NPIP; 0.6 microgram/day) and N-nitrosopyrrolidine (NPYR; 0.4 microgram/day) were also present in one sample. S.mansoni infected subjects showed significantly (P < 0.001) higher levels of 2.9 +/- 2.9 micrograms/day NDMA and a higher frequency of NPIP (in 40/65 samples; 0.4 +/- 0.3 microgram/day) and NPYR occurrence (in 59/65 samples; 0.9 +/- 0.9 microgram/day). Significant further increases in the excretion of volatile N-nitroso compounds were found in S.haematobium-infected patients with mean daily excretion of 19.2 +/- 21 micrograms/day NDMA (in all samples; P < 0.001), 1.6 +/- 2.3 micrograms/day NPIP (in 56/79 samples; P < 0.001) and 1.3 +/- 1.9 micrograms/day NPYR (in 58/79 samples; P < 0.1). The differences either in salivary nitrite/nitrate or in urinary nitrite between the three distinct groups were not significant. However, the urinary excretion of nitrate was elevated from 139 +/- 82 mg/day in the control group to 249 +/- 126 mg/day in S.mansoni infected patients (P < 0.001) and to 174 +/- 176 mg/day in S.haematobium infected subjects (P < 0.005 in comparison to S.mansoni infected group). These results suggest a possible role of N-nitroso compounds in the etiology of schistosome-associated bladder cancer and imply a partial participation of S.mansoni in the multistage process of urinary schistosomiasis-associated bladder carcinogenesis.

Chronic bacterial and parasitic infections and cancer: a review

“…Ovarian carcinoma Ocular lymphoma High [7,[23][24][25][26][27][28][29] Low [30] Low [33] Mycobacterium tuberculosis Lung carcinoma Kaposi"s sarcoma Low [38][39][40][41][42][43] Low [44,45] Schistosoma species [54][55][59][60][61][62][63][64][65][66][67]73] Low [56,[74][75][76][77][78] Low [70] Low [80] Low [81][82] Tropheryma whippelii Lymphoma Gastric adenocarcinoma Low [108] Low [110] Liver flukes 1.Opisthorchis viverrini 2. Clonorchis sinensis…”

Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis

“…9 N-Nitroso compounds are also suspected etiologic agents in the process of bladder carcinoma induction because of Schistosomiasis. 10 Elevated levels of DNA alkylation damage have been detected in Schistosoma-infected carcinomas with high frequencies of G to A transition mutations in the H-ras gene and in the CpG sequences of the p53 tumor suppressor gene. 9 However, the deposition of enormous number of eggs in the bladder subepithelial tissues of infected individuals leads to chronic inflammation that can lead to other complications such as fibrosis, stenosis, and urine retention, usually accompanied by secondary bacterial infection.…”

Bladder Tumor Contains Higher N7-Methylguanine Levels in DNA than Adjacent Normal Bladder Epithelium

“…The source of these agents remains to be determined. It is known that urine samples from subjects infected with S. haematobium contain N-nitroso compounds that can methylate DNA (11,12), and in one experimental study, increasing multiplicity of infection led to increasing levels of O 6 -alkylguanine in host mouse liver DNA (24). Adduct levels were similar in patients with or without infection but this may reflect the limited power of the study to examine the relationship between adducts and S. haematobium infection as most subjects were infected.…”

“…Although apparently innocuous, N7-alkylguanine lesions are used as monitors of exposure to N-nitroso compounds, in part because of their relatively high levels in DNA and also because their repair rate is very much slower than that of other promutagenic and carcinogenic lesions such as O 6 -alkylguanine (10). Nitrosamines have been detected in urine from S. haematobium -infected patients including those with bladder cancer at levels significantly higher than in uninfected individuals (11,12). As this might potentially lead to increased DNA alkylation in bladder DNA and hence bladder cancer, we have examined whether DNA damage (N7-methylguanine) can be detected in DNA from normal bladder tissue and from bladder tumors.…”