Nitrite from inflammatory cells—A cancer risk factor in ulcerative colitis?

Abstract

Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells.

On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease

“…These results appear to be of particular relevance in the context of concerns that the nitrite produced during inflammatory conditions in the gut may enhance, via formation of carcinogenic N-nitrosamines, the risk for colon cancer 61,62 . Of note, nitrite has recently been suggested to modulate T-cell function and cytokine release 63 .…”

Bacterial biota in the human distal esophagus

“…Bacterial populations in other parts of the digestive system, including the oral cavity and colon, play important roles in the maintenance of local physiology as well as in disease etiology (1)(2)(3)(4)(5)(6)(7)33). A full assessment of the composition, transience, or stability of this complex bacterial biota in the distal esophagus and associations with disease remains to be determined.…”

“…Conversely, loss of normal biota is responsible for overgrowth of opportunistic pathogens that normally are inhibited, such as occurs in antibiotic-associated colitis (3). Microenvironment alterations may favor overgrowth of bacteria that produce carcinogenic metabolites (4,5), promoting tumorigenesis in inflammation-induced cancers, such as adenocarcinoma in mouse experimental colitis models (6).…”

Quantitation of Four Guanine Oxidation Products from Reaction of DNA with Varying Doses of Peroxynitrite

“…Inflammatory cells such as neutrophils and macrophages, which are capable of simultaneously producing nitric oxide and superoxide, can therefore generate ONOO − in vivo. In chronic inflammatory states, these cells can overproduce ONOO − over prolonged periods of time, and excess ONOO − formation has been implicated in a number of pathological conditions such as rheumatoid arthritis and neurodegenerative diseases (2)(3)(4) as well as in increased cancer risk (5). In addition to reacting with a number of cellular substrates, ONOO − reacts with DNA, resulting in both sugar (6)(7)(8) and nucleobase damage.…”