Inhibition of nitrosamine formation by ascorbic acid: participation of free radicals in its anaerobic reaction with nitrite

Kalus, W. H.; Filby, W. G.

doi:10.1007/bf01953698

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…For example, vitamin C and vitamin E have been shown to inhibit the formation of N-nitroso compounds from nitrate in human subjects [ 68 ]. Food components, such as vitamins C and E, may exert an inhibitory effect in cancer carcinogenesis by blocking the nitrosation process by quenching free radicals in their anaerobic reaction with nitrite, thus reducing the endogenous synthesis of NOCs [ 69 ]. Further studies with large sample size and sufficient statistical power are required to confirm or refute these findings.…”

Section: Discussionmentioning

confidence: 99%

Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

Xie

Jia

et al. 2016

Oncotarget

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Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted.Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.

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Section: Discussionmentioning

confidence: 99%

Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

Xie

Jia

et al. 2016

Oncotarget

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“…Protein has been suggested to be the main source of secondary and tertiary amines ( 32 , 33 ) , the indispensable agents for the nitrosation reaction. However, vitamins C and E may exert an inhibitory effect in cancer carcinogenesis by blocking the nitrosation process by quenching free radicals in their anaerobic reaction with nitrite ( 34 ) , thus reducing the endogenous synthesis of NOC ( 8 , 11 ) . Similar patterns have been reported in other investigations ( 20 , 32 , 35 , 36 ) .…”

Section: Discussionmentioning

confidence: 99%

DietaryN-nitroso compounds and risk of colorectal cancer: a case–control study in Newfoundland and Labrador and Ontario, Canada

et al. 2013

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Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador, and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95% CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest vs lowest quintiles, OR: 1.42; 95% CI: 1.03,1.96; p-trend=0.005), specifically for rectal carcinoma (OR: 1.61; 95% CI: 1.11,2.35; p-trend=0.01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR: 1.47; 95% CI: 1.03,2.10; p-trend=0.20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and vitamin E intakes (OR:3.01; 95% CI: 1.43,6.51; p-interaction=0.017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.

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“…The saliva accounts for about 40 mg/day and the rest is from gastric juice (5-10 mg of urate per liter), bile, and pancreatic and intestinal juices (34). Ascorbate is known to be effective as a trap for nitrosating radicals derived from nitrite (51), which can form carcinogenic nitrosamines from secondary amines at the acidic pH of the stomach, and urate might be equally effective. Urate is an effective antioxidant at alkaline and neutral pH (52) and in acid; a standard method for its analysis involves its use as a reductant of the acid phosphotungstate complex to form a blue color (53).…”

Section: Methodsmentioning

confidence: 99%

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Ames¹,

Cathcart²,

Schwiers³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

2,503

1,609

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During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one ofthese protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate level in humans (about 300 ILM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.Toxicity by oxygen radicals has been suggested as a major cause of cancer, heart disease, and aging (1-13). Oxygen radicals and other oxidants appear to be toxic in large part because they initiate the chain reaction of lipid peroxidation (rancidity). Lipid peroxidation generates various reactive species-such as radicals, hydroperoxides, aldehydes, and epoxides-with the capability of causing damage to DNA, RNA, proteins, cellular membranes, and cellular organization. Aerobic organisms have an array of protective mechanisms both for preventing the formation of oxidants and lipid peroxidation and for repairing oxidative damage. The protective systems include enzymes, such as superoxide dismutase (12) and the selenium-containing glutathione peroxidase (9, 10), and antioxidants and radical scavengers, such as a-tocopherol (vitamin E) and a-carotene in the lipid portion ofthe cell and glutathione and ascorbic acid in the aqueous phase (9, 10). These protective mechanisms are now being recognized as anticarcinogenic and, in some cases, even as life-span extending (5-7).A marked increase in life-span has occurred in human evolution during the descent from prosimians over the past 60 million years (4). At the same time an enormous decrease in the age-specific cancer rate has occurred in humans compared to short-lived mammals (14, 15). It seems likely that a major factor in lengthening life-span and decreasing age-specific cancer rates may have been the evolution ofeffective protective mechanisms against oxygen radicals (2-7, 10). We propose that one such mechanism is high plasma uric acid. MATERIALS AND METHODS'y-Ray Irradiation. Solutions of substrate (0.3 mM) in potassium phosphate buffer (20 mM, pH 7.4) were purged with 2, N2, or N20, sealed, and irradiated at room temperature with a 60Co y-ray source [12.7 krads/mi...

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Inhibition of nitrosamine formation by ascorbic acid: participation of free radicals in its anaerobic reaction with nitrite

Cited by 10 publications

References 21 publications

Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

DietaryN-nitroso compounds and risk of colorectal cancer: a case–control study in Newfoundland and Labrador and Ontario, Canada

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

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