Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats

S. S. Mirvish, Q. Huang, S. C. Chen, D. F. Birt, G. W B Clark, R. A. Hinder, Thomas Christopher Smyrk, T. R. DeMeester

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29 Citations (Scopus)

Abstract

The mechanism is discussed by which certain nitrosamines induce esophageal papillomas and squamous cancer in rats, and some evidence is presented for the view that nitrosamines also induce the same cancer in humans, especially in China and South Africa. Studies on the metabolism of nitrosamines by cytochrome P450 isozymes in rat and human esophagus, including the activation reactions of formaldehyde and pentaldehyde formation from methyl-n-amylnitrosamine (MNAN), are reviewed. These reactions are catalyzed by microsomes from the rat and human esophagus, probably because these microsomes contain specific cytochrome P450 isozymes. Evidence is reviewed for the occurrence of nitrosamines related to MNAN in fungus-infected corn. The incidence of esophageal adenocarcinoma is rising in Western countries. The precursor lesion, Barrett's esophagus, is associated with colon cancer, suggesting a role for bile salts in the induction of the esophageal tumor. Studies are described in which rats were subjected to esophago-duodenostomy (joining the duodenum to the esophagus) and then treated with nitrosamines that normally induce esophageal squamous cancer. Adenocarcinomas of the lower esophagus were induced as well as Barrett's esophagus (under one set of conditions). Feeding a high-fat diet with this system increased the incidence of esophageal adenocarcinoma. This tumor was not induced when the operation was changed to esophago-gastroplasty (widening the lower esophageal sphincter). These results support a role of reflux of duodenal contents (including bile and pancreatic juice) rather than of gastric contents in the etiology of human esophageal adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)627-631
Number of pages5
JournalEndoscopy
Volume25
Issue number9
StatePublished - 1993
Externally publishedYes

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Nitrosamines
N-amyl-N-methylnitrosamine
Esophagus
Adenocarcinoma
Barrett Esophagus
Microsomes
Cytochrome P-450 Enzyme System
Isoenzymes
Neoplasms
Duodenostomy
Duodenogastric Reflux
Gastroplasty
Pancreatic Juice
Lower Esophageal Sphincter
Gastrointestinal Contents
Incidence
Papilloma
High Fat Diet
Esophageal Neoplasms
South Africa

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Mirvish, S. S., Huang, Q., Chen, S. C., Birt, D. F., Clark, G. W. B., Hinder, R. A., ... DeMeester, T. R. (1993). Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats. Endoscopy, 25(9), 627-631.

Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats. / Mirvish, S. S.; Huang, Q.; Chen, S. C.; Birt, D. F.; Clark, G. W B; Hinder, R. A.; Smyrk, Thomas Christopher; DeMeester, T. R.

In: Endoscopy, Vol. 25, No. 9, 1993, p. 627-631.

Research output: Contribution to journalArticle

Mirvish, SS, Huang, Q, Chen, SC, Birt, DF, Clark, GWB, Hinder, RA, Smyrk, TC & DeMeester, TR 1993, 'Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats', Endoscopy, vol. 25, no. 9, pp. 627-631.
Mirvish SS, Huang Q, Chen SC, Birt DF, Clark GWB, Hinder RA et al. Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats. Endoscopy. 1993;25(9):627-631.
Mirvish, S. S. ; Huang, Q. ; Chen, S. C. ; Birt, D. F. ; Clark, G. W B ; Hinder, R. A. ; Smyrk, Thomas Christopher ; DeMeester, T. R. / Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats. In: Endoscopy. 1993 ; Vol. 25, No. 9. pp. 627-631.
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