Mechanisms of Disease: Carcinogenesis in Barrett's Esophagus

Navtej S Buttar; Kenneth K Wang


Nat Clin Pract Gastroenterol Hepatol. 2004;1(2) 

In This Article

Carcinogen Exposure

The effects of carcinogen exposure on the development of esophageal adenocarcinoma have not been extensively studied, although pre-clinical animal studies and epidemiological evidence indicate that there might be a link between the two.[36,37] In rodents and mice that had surgical interventions carried out to cause reflux of gastroduodenal contents into the esophagus, the rate of esophageal adenocarcinoma development increased after administration of carcinogens, such as 2,6-dimethylnitrosomorpholin or N-methyl-N-benzylnitrosamine.[37] The importance of this is twofold. First, patients with ACHLORHYDRIA that is induced by PPI use, atrophic gastritis or gastric surgery have overgrowth of nitrate-reducing bacteria in the upper gut,[38,39] and these bacteria could convert dietary nitrate to nitrite. Second, in the latter half of the twentieth century, there was a rapid increase in the use of nitrate-based fertilizers. This resulted in a marked increase in nitrate levels in leafy vegetables and drinking water.[39] Most ingested nitrates are excreted, but a significant amount are concentrated by the salivary glands and secreted into the mouth.[40] Oral microbes on the tongue reduce the salivary nitrates to nitrites.[40] When these nitrites come into contact with contents of gastroduodenal reflux in the lower esophagus, they change to nitrous acid that decomposes immediately into nitric oxide.[41] Nitric oxide has been linked to early events in the tumorigenic process, including DNA damage, lipid peroxidation, regulation of inflammation and carcinogenesis.[42]


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