Abstract
The aim of this article is to review the current experimental knowledge of mutagenesis in Barrett’s esophagus (BE) with special emphasis on the effect of bile salts and acid. Human evidence of direct mutagenicity is rare. Only the correlation of increased quantities and a change in the quality of bile salts with the complications of duodenogastric reflux such as BE and esophageal adenocarcinoma as an indirect marker of mutagenicity has been shown in several studies. Further evidence comes from p53 studies demonstrating an increased number of mutated p53 genes in patients with BE, esophageal adenocarcinoma, or both. Most animal and cellular experiments are carried out in a neutral pH environment, not reflecting the true nature of a reflux episode. The few studies using moderate low acid reflux conditions in combination with bile salts demonstrated a combined effect on mutagenicity. Our current knowledge of bile salt mutagenicity is predominantly based on experiments with hepatocytes and colon cancer cell lines. Future studies must be aimed at esophageal cell lines, cultured Barrett’s tissue, and esophageal adenocarcinoma cell lines.
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References
DC Gotley AP Morgan MJ Cooper (1988) ArticleTitleBile acid concentrations in the refluxate of patients with reflux oesophagitis Br. J. Surg. 754 587–590
WKH Kauer JH Peters TR DeMeester et al. (1995) ArticleTitleMixed reflux of gastric juice is more harmful to the esophagus than gastric juice alone: the need for surgical therapy reemphasized Ann. Surg. 222 525–531 Occurrence Handle1:STN:280:BymD38rht1c%3D Occurrence Handle7574932
SY Iftikhar S Ledingham RJ Steele (1993) ArticleTitleBile reflux in columnar lined Barrett’s esophagus Ann. R. Coll. Surg. Engl. 75 411–416 Occurrence Handle1:STN:280:ByuC3Mzltl0%3D Occurrence Handle8285543
HJ Stein WKH Kauer H Feussner et al. (1998) ArticleTitleBile reflux in benign and malignant Barrett’s esophagus: effect of medical acid suppression and fundoplication J. Gastrointest. Surg. 2 333–341 Occurrence Handle10.1016/S1091-255X(98)80072-3 Occurrence Handle1:STN:280:DyaK1M%2FlvF2ktA%3D%3D Occurrence Handle9841990
S Kraehenbühl C Talos S Fischer et al. (1994) ArticleTitleToxicity of the bile acids on the electron transport chain of isolated rat liver mitochondria Hepatology 19 471–479 Occurrence Handle7904981
JR Spivey SF Bronk GJ Gores (1993) ArticleTitleGlycochenodeoxycholate induced lethal cell injury in rat hepatocytes J. Clin. Invest. 92 17–24 Occurrence Handle1:CAS:528:DyaK3sXlsFOns7Y%3D Occurrence Handle8325981
IC Hsu RA Metcalf T Sun et al. (1991) ArticleTitleMutational hotspot in the p53 gene in human hepatocellular carcinomas Nature 350 427–428 Occurrence Handle1:CAS:528:DyaK3MXitVSqs7g%3D Occurrence Handle1849234
M Otzurk (1991) ArticleTitlep53 mutation in heptocellular carcinoma after aflatoxin exposure Lancet 338 1356–1359 Occurrence Handle1:CAS:528:DyaK38XktVanu7g%3D Occurrence Handle1682737
MS Greenblat WP Bennett M Hollstein et al. (1994) ArticleTitleMutations in the p53 tumor supressor gene: clues to cancer etiology and molecular pathogenesis Cancer Res. 54 4855–4878 Occurrence Handle8069852
MC Hollstein L Peri AM Mandard et al. (1991) ArticleTitleGenetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations Cancer Res. 51 4102–4106 Occurrence Handle1:CAS:528:DyaK3MXmtVSjsrk%3D Occurrence Handle1855226
HJ Stein WKH Kauer H Feussner et al. (1999) ArticleTitleBile acids as components of the duodenogastric refluxate: detection, relationship to bilirubin, mechanism of injury and clinical relevance Hepatogastroenterology. 46 66–73 Occurrence Handle1:CAS:528:DyaK1MXitFyksb8%3D Occurrence Handle10228767
RC Fitzgerald MB Omary G Triadafilopoulos (1996) ArticleTitleDynamic effects of acid on Barrett’s esophagus: an ex vivo proliferation and differentiation model J. Clin. Invest. 98 2120–2128 Occurrence Handle1:CAS:528:DyaK28XmvVequ70%3D Occurrence Handle8903332
KD Lillimoe LF Johnson JW Harmon (1982) ArticleTitleRole of the components of gastroduodenal contents in experimental acid esophagitis Surgery 91 276–284
KD Lilimoe LF Johnson JW Harmon (1983) ArticleTitleAlkaline esophagitis: a comparison of the ability of components of gastroduodenal contents to injure the rabbit esophagus Gastroenterology 85 621–628 Occurrence Handle6307806
D Armstrong ERC Rytina GM Murphy et al. (1994) ArticleTitleGastric mucosal toxicity of duodenal juice constituents in the rat Dig. Dis. Sci. 39 327–329 Occurrence Handle1:CAS:528:DyaK2cXjt1SmtLk%3D Occurrence Handle8313815
H Arndt F Kullmann J Schölmerich et al. (1997) ArticleTitleAcute and chronic effects of different bile acids on indomethacin induced intestinal inflammation Inflammation 21 553–567 Occurrence Handle1:CAS:528:DyaK1cXisFSnsw%3D%3D Occurrence Handle9429904
WA Faubion PJ Roberts SF Bronk et al. (1998) ArticleTitleA caspase 8-cathepsin B protease cascade contributes to bile salt induced hepatocyte apoptosis Gastroenterology 114 L0168
J Rockett K Larkin J Darnton et al. (1997) ArticleTitleFive newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization Br. J. Cancer 75 258–263 Occurrence Handle1:STN:280:ByiC28zitVQ%3D Occurrence Handle9010035
H Garewal H Bernstein C Bersstein et al. (1996) ArticleTitleReduced bile acid induced apoptosis in normal colorectal mucosa: a potential biological marker for cancer risk Cancer Res. 56 1480–1483 Occurrence Handle1:CAS:528:DyaK28XitVems7Y%3D Occurrence Handle8603388
SS Mirvish Q Huang SC Chen et al. (1993) ArticleTitleMetabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats Endoscopy 25 627–631 Occurrence Handle1:STN:280:ByuC28vgvVI%3D Occurrence Handle8119218
SEA Attwood TC Smyrk TR DeMeester et al. (1992) ArticleTitleDuodenoesophageal reflux and the development of esophageal adenocarcinoma in rats Surgery 111 503–510 Occurrence Handle1:STN:280:By2B1crotlQ%3D Occurrence Handle1598670
M Pera A Cardesa JA Bombi et al. (1989) ArticleTitleInfluence of esophago-duodenostomy on the induction of adenocarcinoma of the distal esophagus in Sprague-Dawley rats by the subcutaneous injection of 2,6-dimethylnitrosmorpholine Cancer Res. 49 6803–6808 Occurrence Handle1:STN:280:By%2BD2Mflt10%3D Occurrence Handle2819720
A Ireland JH Peters TC Smyrk et al. (1996) ArticleTitleGastric juice protects against the development of esophageal adenocarcinoma in the rat Ann. Surg. 224 358–371 Occurrence Handle10.1097/00000658-199609000-00012 Occurrence Handle1:STN:280:BymH3cfitF0%3D Occurrence Handle8813264
J Theisen JH Peters M Hughes et al. (1998) ArticleTitleBile salt induced mutation in vitro Gastroenterology 115 A963
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Theisen, J., Peters, J. & Stein, H. Experimental Evidence for Mutagenic Potential of Duodenogastric Juice on Barrett’s Esophagus. World J. Surg. 27, 1018–1020 (2003). https://doi.org/10.1007/s00268-003-7055-z
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DOI: https://doi.org/10.1007/s00268-003-7055-z