Urinary N-Nitrosamino Acids as Indices of Endogenous Formation of N-Nitroso Compounds

Ohshima, Hiroshi; Pignatelli, Brigitte; Nair, Jagadeesan; Muñóz, Núbia; Calmels, S.; Crespi, Massimo; Lu, Shih-Hsin; Bhide, S. V.; Vincent, P; Leclerc, H; Kamiyama, Sigetosi; Bartsch, Helmut

doi:10.1007/978-1-4615-9462-8_47

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…These particular NOC have therefore been extensively used to monitor endogenous N -nitrosation in the human gastrointestinal tract. In volunteers, ingestion of nitrate has been demonstrated to lead to enhanced urinary excretion of N -nitrosated amino acids (Ohshima and Bartsch 1988 ; Ohshima et al 1982a ; Tricker and Preussmann 1987 ).…”

Section: Exposure To N -Nitrosating Agents: the Co...mentioning

confidence: 99%

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food

Eisenbrand,

Buettner,

Diel

et al. 2024

Arch Toxicol

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Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2–3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment.

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Section: Exposure To N -Nitrosating Agents: the Co...mentioning

confidence: 99%

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food

Eisenbrand,

Buettner,

Diel

et al. 2024

Arch Toxicol

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“…NPRO with ASC/NPRO without ASC is defined as the excretion of NPRO after proline loading with ASC divided by that after proline loading without ASC in urine. A value of NPRO with ASC/NPRO without ASC <1 means that the endogenous formation of NPRO can be inhibited by ASC 16, 17. Statistical analysis involved several different methods.…”

Section: Methodsmentioning

confidence: 99%

Estimation of the potential for nitrosation and its inhibition in subjects from high‐ and low‐risk areas for esophageal cancer in southern China

Lin

Shen

et al. 2003

Intl Journal of Cancer

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We studied 2 counties in southern China, which are close to each other but show very different mortality rates from esophageal cancer. We collected 12 hr urine samples and analyzed them for NPRO, other nitrosamino acids, nitrate and ASC. The potential for forming NPRO and the effect on inhibition by ASC were recorded. Urine was collected after (i) no treatment, (ii) a dose of proline and (iii) proline with ASC. Intake and excretion of nitrate were significantly greater in the high-risk area. After the proline dose, urinary excretion of NPRO was significantly greater in the high-risk area. The inhibitory effect of ASC after taking it with proline was less in the high-risk area. Hence, the high-risk area showed greater potential for forming NPRO, and this formation was less inhibited by ASC. 5 in women), 7 times the average rate in China, and has persistently remained high. However, Lufeng County on the coastal area, about 80 km from Nan'ao, shows a very different mortality rate (10/10 5 ). We also found that the TNOC detection rate in the diet, TNOC daily intake and urinary excretion and daily intake of volatile nitrosamines in Nan'ao were significantly greater than values in Lufeng. 3 There was powerful synthesis of N-nitrosopiperidine in the Nan'ao diet after cultivation with sodium nitrite at 37°C for 4 hr. 4 Most NOCs are strong carcinogens in animals and may play an important part in the etiology of esophageal cancer in northern China, 5-10 but there remains a lack of confirmed evidence. The human body contacts NOCs by exogenous exposure and endogenous synthesis. The latter may be the main contact pathway in humans. The urinary NPRO model is a sensitive method for estimating the potential for forming NPRO in vivo. Hence, we believe that the NOC effect on the etiology of esophageal cancer should receive the most attention. In this report, we compared the differences in potential for forming NOCs in vivo and the effect on inhibiting this formation by ASC between Nan'ao and Lufeng subjects, to further evaluate the effects of NOC endogenous formation on the etiology of esophageal cancer and to provide meaningful clues for taking preventive measures. MATERIAL AND METHODS Chemicals and reagentsThe 5 NAAs used as standards were obtained from the Chinese Academy of Medical Science (Beijing, People's Republic of China), which synthesized and ascertained the standards. 9 NAA standards were NPIC, NPRO, NTCA, NMTCA and NSAR. L-Proline and ASC were obtained from Sigma (St. Louis, MO). Diazomethane was prepared by the action of potassium hydroxide on Nnitroso-N-methyl-p-toluenesulfonamide (Merck, Darmstadt, Germany) in ether. Cadmium powder for reducing nitrate to nitrite was obtained from Wako (Osaka, Japan). All other reagents were commercially available and used without further purification. Study subjects and sample collectionNan'ao County and Lufeng County were selected, respectively, as high-and low-risk areas for esophageal cancer. The distance between Nan'ao and the mainland is about 8 km, and Lufeng is situated o...

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“…Beyond undergoing enterosalivary circulation, nitrosatable food constituents may be prone to endogenous N -nitrosation when encountering nitrosating agents anywhere in the body. For the gastrointestinal tract, endogenous NOC formation has been exemplified especially for secondary amino acids such as proline, hydroxyproline (Ohshima et al 1982 ) as well as thiazolidine-4-carboxylic acids and congeners (Ohshima and Bartsch 1988 ; Ohshima et al 1984 ). The corresponding NOC, formed from the respective amino acids following nutritional uptake and/or during digestion, are excreted fairly quantitatively in the urine and are not carcinogenic.…”

Section: Process-related Contaminantsmentioning

confidence: 99%

The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment

et al. 2022

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The “totality” of the human exposure is conceived to encompass life-associated endogenous and exogenous aggregate exposures. Process-related contaminants (PRCs) are not only formed in foods by heat processing, but also occur endogenously in the organism as physiological components of energy metabolism, potentially also generated by the human microbiome. To arrive at a comprehensive risk assessment, it is necessary to understand the contribution of in vivo background occurrence as compared to the ingestion from exogenous sources. Hence, this review provides an overview of the knowledge on the contribution of endogenous exposure to the overall exposure to putative genotoxic food contaminants, namely ethanol, acetaldehyde, formaldehyde, acrylamide, acrolein, α,β-unsaturated alkenals, glycation compounds, N-nitroso compounds, ethylene oxide, furans, 2- and 3-MCPD, and glycidyl esters. The evidence discussed herein allows to conclude that endogenous formation of some contaminants appears to contribute substantially to the exposome. This is of critical importance for risk assessment in the cases where endogenous exposure is suspected to outweigh the exogenous one (e.g. formaldehyde and acrolein).

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Urinary N-Nitrosamino Acids as Indices of Endogenous Formation of N-Nitroso Compounds

Cited by 3 publications

References 12 publications

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food

Estimation of the potential for nitrosation and its inhibition in subjects from high‐ and low‐risk areas for esophageal cancer in southern China

The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment

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