Nitrite Promotes Lymphoma Incidence in Rats

Newberne, Paul M.

doi:10.1126/science.451551

Cited by 72 publications

(15 citation statements)

References 14 publications

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“…N-nitrosoamines, which react with nucleic acids, are highly carcinogenic in laboratory animals (Gangolli et al, 1994) and could also be associated with human cancer (Bartsch and Montesano, 1984;Craddock, 1983). A report published in 1979 that dietary nitrite caused lymphomas in rats (Newberne, 1979) (Speijers and Brandt, 2003). Indeed, a diet rich fruit and vegetables, which far exceeds the WHO acceptable daily intake of nitrate, is not associated with an increase in deaths from cancer (Hung et al, 2004).…”

Section: Potential For Detrimental Effects Of High Nitrate Intakementioning

confidence: 97%

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Bondonno

Croft

Hodgson

2015

Critical Reviews in Food Science and Nutrition

106

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Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine-NO-synthase pathway and the recently discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.

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Section: Potential For Detrimental Effects Of High Nitrate Intakementioning

confidence: 97%

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Bondonno

Croft

Hodgson

2015

Critical Reviews in Food Science and Nutrition

106

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“…In the late 1970s, researchers found that ingestion of nitrite could cause tumours in rats 20. After some initial debate regarding the mechanism,21 a theory to explain the carcinogenic effects of nitrite emerged.…”

Section: Nitrosamines and Cancermentioning

confidence: 99%

Biology of nitrogen oxides in the gastrointestinal tract

Lundberg

Weitzberg

2012

Gut

160

103

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Throughout the human gastrointestinal tract a variety of reactive nitrogen oxides are continuously formed as a result of a complex interplay between the host, commensal bacteria and dietary factors. These compounds include nitric oxide, nitrite, nitrate, peroxynitrite, S-nitrosothiols, nitrated fatty acids and N-nitrosamines, all of which are bioactive with the potential to affect physiological and pathological processes locally in the gut as well as systemically after absorption. Historically, the literature has been dominated by studies on the formation of potentially carcinogenic nitrosamines, but the focus was shifted in the 1980s with the seminal discovery of the L-arginine-nitric oxide pathway and its profound impact on normal physiological functions. More recently, a nitrate-nitrite-nitric oxide pathway has been discovered, with implications for local host defence and gut mucosal integrity and, intriguingly, also for systemic regulation of cardiovascular and metabolic function. This review discusses recent advances in the understanding of the formation, biochemistry, physiology and pathophysiology of reactive nitrogen oxides in the gastrointestinal tract. In addition, opportunities for nitric oxide-based pharmacological or dietary interventions are highlighted.

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“…A Food and Drug Administration (FDA)-supported study reported that nitrite doubles the risk of lymphomas in rat 62 and suggested that it increased cancer incidence and tumor growth rate in animal studies 91 . Nevertheless, the human studies did not clarify this issue.…”

Section: Nitrite On Demand Local But Systemically Administered No Dmentioning

confidence: 99%

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Pluta

2006

Neurological Research

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Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation and chemoregulation. Subarachnoid hemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space, destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase in the endogenous competitive NOS inhibitor, asymmetric dimethylarginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in cerebrospinal fluid (CSF) in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination owing to disappearance of ADMA-hydrolyzing enzyme [dimethylarginine dimethylaminohydrolase II (DDAH II)] immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of pre-clinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability.

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Nitrite Promotes Lymphoma Incidence in Rats

Cited by 72 publications

References 14 publications

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Biology of nitrogen oxides in the gastrointestinal tract

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

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