Skip to main content

Folsäure und Ursodesoxycholsäure

  • Conference paper
  • 94 Accesses

Part of the book series: Gastroenterologie Update ((GASTROUPDATE,volume 2002))

Zusammenfassung

In der Vergangenheit wurde die Rolle des B-Vitamins Folsäure im Wesentlichen in der Prävention der megaloblastischen Anämie gesehen. Aktuell wird den Folaten deutlich größere Aufmerksamkeit geschenkt, da gezeigt werden konnte, dass sie in der Lage sind, fetale Malformationen, wie z. B. Spina bifida, zu verhindern und womöglich in der Risikoreduktion von kardiovaskulären Erkrankungen, die durch eine Homozysteinämie vermittelt wird, von Bedeutung zu sein. Inzwischen liegen vermehrte Evidenzen vor, dass Folate auch eine signifikante Rolle in der Pathogenese von Neoplasien unterschiedlichster Organe, hier insbesondere des Kolorektums, eine Rolle spielen.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Barone M, Francavilla A, Polimeno L, Ierard E, Romanelli D, Berloco P et al. (1996) Modulation of rat hepatocyte proliferation by bile salts: in vitro and in vivo studies. Hepatology 23:1159–1166

    PubMed  CAS  Google Scholar 

  • Baylin SB, Makos M, Wu JJ, Yen RW, de Bustros A, Vertino P et al. (1991) Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 3(10): 383–390

    PubMed  CAS  Google Scholar 

  • Benito E, Stiggelbout A, Bosch FX, Obrador A, Kaldor J, Mulet M et al. (1991) Nutritional factors in colorectal Cancer risk: a case-control study in Majorca. Int J Cancer 49(2): 161–167

    Article  PubMed  CAS  Google Scholar 

  • Benito E, Cabeza E, Moreno V, Obrador A, Bosch FX (1993) Diet and colorectal adenomas: a case-control study in Majorca. Int J Cancer 55(2): 213–219

    Article  PubMed  CAS  Google Scholar 

  • Biasco G, Zannoni U, Paganelli GM, Santucci R, Gionchetti P, Rivolta G et al. (1997) Folie aeid supplementation and cell kinetics of rectal mueosa in patients with ulcerative Colitis. Cancer Epidemiol Biomarkers Prev 6(6): 469–471

    PubMed  CAS  Google Scholar 

  • Bird CL, Swendseid ME, Witte JS, Shikany JM, Hunt IF, Frankl HD et al. (1995) Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 4(7): 709–714

    PubMed  CAS  Google Scholar 

  • Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G et al. (1997) Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for Cancer and neuronal damage. Proc Natl Acad Sci USA 94(7): 3290–3295

    Article  PubMed  CAS  Google Scholar 

  • Botla R, Spivey JR, Aguilar H, Bronk SF, Gores GJ. (1995) Ursodeoxycholate (UDCA) inhibits the mitochondrial membrane permeability transition induced by glycochenodeoxycholate: a mechanism of UDCA cytoprotection. J Pharmacol Exp Ther 272(2): 930–938

    PubMed  CAS  Google Scholar 

  • Brentnall TA, Haggitt RC, Rabinovitch PS, Kimmey MB, Bronner MP, Levine DS et al. (1996) Risk and natural history of colonic neoplasia in patients with primary sclerosing Cholangitis and ulcerative Colitis. Gastroenterology 110(2): 331–338

    Article  PubMed  CAS  Google Scholar 

  • Broome U, Lofberg R, Veress B, Eriksson LS (1995) Primary sclerosing Cholangitis and ulcerative Colitis: evidence for increased neoplastic potential. Hepatology 22(5): 1404–1408

    PubMed  CAS  Google Scholar 

  • Cabral DJ, Small DM, Lilly HS, Hamilton JA (1987) Transbilayer movement of bile aeids in model membranes. Biochemistry 26(7): 1801–1804

    Article  PubMed  CAS  Google Scholar 

  • Cheah PY, Bernstein H (1990) Modifikation of DNA by bile aeids: a possible factor in the etiology of colon Cancer. Cancer Lett 49:207–210

    Article  PubMed  CAS  Google Scholar 

  • Cheng P, Schmutte C, Cofer KF, Felix JC, Yu MC, Dubeau L (1997) Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis. Br J Cancer 75(3): 396–402

    Article  PubMed  CAS  Google Scholar 

  • Cravo M, Fidalgo P, Pereira AD, Gouveia-Oliveira A, Chaves P, Seihub J et al. (1994) DNA methylation as an intermediate biomarker in colorectal Cancer: modulation by folic aeid supplementation. Eur J Cancer Prev 3(6): 473–479

    Article  PubMed  CAS  Google Scholar 

  • Cravo M, Pinto R, Fidalgo P, Chaves P, Gloria L, Nobre-Leitao C et al. (1996) Global DNA hypomethylation oecurs in the early stages of intestinal type gastric Carcinoma. Gut 39(3): 434–438

    Article  PubMed  CAS  Google Scholar 

  • Cummings JH, Wiggins HS, Jenkins DJ, Houston H, Jivraj T, Drasar BS et al. (1978) Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile aeid, and fat exeretion. J Clin Invest 61(4): 953–963

    Article  PubMed  CAS  Google Scholar 

  • Dizik M, Christman JK, Wainfan E (1991) Alterations in expression and methylation of specific genes in livers of rats fed a Cancer promoting methyl-deficient diet. Carcinogenesis 12(7): 1307–1312

    Article  PubMed  CAS  Google Scholar 

  • Earnest DL, Holubec H, Wali RK, Jolley CS, Bissonette M, Bhattacharyya AK et al. (1994) Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res 54:5071–5074

    PubMed  CAS  Google Scholar 

  • Enstrom JE (1975) Colorectal Cancer and consumption of beef and fat. Br J Cancer 32: 321–329

    Article  Google Scholar 

  • Ferraroni M, La Vecchia C, D’Avanzo B, Negri E, Franceschi S, Decarli A (1994) Selected micronutrient intake and the risk of colorectal Cancer. Br J Cancer 70(6): 1150–1155

    Article  PubMed  CAS  Google Scholar 

  • Fowler BM, Giuliano AR, Piyathilake C, Nour M, Hatch K (1998) Hypomethylation in cervical tissue: is there a correlation with folate Status? Cancer Epidemiol Biomarkers Prev 7(10): 901–906

    PubMed  CAS  Google Scholar 

  • Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G (1991) Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 20(2): 368–374

    Article  PubMed  CAS  Google Scholar 

  • Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B et al. (1999) Dietary fiber and the risk of colorectal Cancer and adenoma in women. N Engl J Med 340(3): 169–176

    Article  PubMed  CAS  Google Scholar 

  • Galle PR, Theilmann L, Raedsch R, Otto G, Stiehl A (1990) Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology 12(3 Pt 1): 486–491

    Article  PubMed  CAS  Google Scholar 

  • Garewal H, Bernstein H, Bernstein C, Sampliner R, Payne C (1996) Reduced bile acidinduced apoptosis in „normal“ colorectal mucosa: a potential biological marker for Cancer risk. Cancer Res 56(7):1480–1483

    PubMed  CAS  Google Scholar 

  • Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopoulos D, Rosner BA et al. (1993) Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 85(11): 875–884

    Article  PubMed  CAS  Google Scholar 

  • Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA et al. (1998) Multivitamin use, folate, and colon Cancer in women in the Nurses’ Health Study. Ann Intern Med 129(7): 517–524

    PubMed  CAS  Google Scholar 

  • Glynn SA, Albanes D, Pietinen P, Brown CC, Rautalahti M, Tangrea JA et al. (1996) Colorectal Cancer and folate Status: a nested case-control study among male smokers. Cancer Epidemiol Biomarkers Prev 5(7): 487–494

    PubMed  CAS  Google Scholar 

  • Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP (1985) Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228(4696): 187–190

    Article  PubMed  CAS  Google Scholar 

  • Hague A, Eider DJ, Hicks DJ, Paraskeva C (1995) Apoptosis in colorectal tumour cells: induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate. Int J Cancer 60(3): 400–406

    Article  PubMed  CAS  Google Scholar 

  • Hill MJ, Drasar BS, Hawksworth G, Aries V, Crowther JS, Williams RE (1971) Bacteria and aetiology of Cancer of large bowel. Lancet 1(7690): 95–100

    Article  PubMed  CAS  Google Scholar 

  • No Hill MJ, Drasar BS, Williams RE, Meade TW, Cox AG, Simpson JE et al. (1975) Faecal bile-acids and Clostridia in patients with Cancer of the large bowel. Lancet 1(7906): 535–539

    Article  Google Scholar 

  • Itzkowitz SH (1997) Inflammatory bowel disease and Cancer. Gastroenterol Clin North Am 26(1): 129–139

    Article  PubMed  CAS  Google Scholar 

  • Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ et al. (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128(7): 1204–1212

    PubMed  CAS  Google Scholar 

  • Jones PA (1996) DNA methylation errors and Cancer. Cancer Res 56(11): 2463–2467

    PubMed  CAS  Google Scholar 

  • Kim YI, Giuliano A, Hatch KD, Schneider A, Nour MA, Dallal GE et al. (1994) Global DNA hypomethylation increases progressively in cervical dysplasia and Carcinoma. Cancer 74(3): 893–899

    Article  PubMed  CAS  Google Scholar 

  • Kim YI, Christman JK, Fleet JC, Cravo ML, Salomon RN, Smith D et al. (1995) Moderate folate deficiency does not cause global hypomethylation of hepatic and colonic DNA or c-myc-specific hypomethylation of colonic DNA in rats. Am J Clin Nutr 61(5): 1083–1090

    PubMed  CAS  Google Scholar 

  • Kim YI, Pogribny IP, Basnakian AG, Miller JW, Seihub J, James SJ et al. (1997) Folate deficiency in rats induces DNA Strand breaks and hypomethylation within the p53 tumor suppressor gene. Am J Clin Nutr 65(1): 46–52

    PubMed  CAS  Google Scholar 

  • Kim YI, Fawaz K, Knox T, Lee YM, Norton R, Arora S et al. (1998) Colonic mucosal concentrations of folate correlate well with blood measurements of folate Status in persons with colorectal polyps. Am J Clin Nutr 68(4): 866–872

    PubMed  CAS  Google Scholar 

  • Kim YI, Shirwadkar S, Choi SW, Puchyr M, Wang Y, Mason JB (2000) Effects of dietary folate on DNA Strand breaks within mutation-prone exons of the p53 gene in rat colon. Gastroenterology 119(1): 151–161

    Article  PubMed  CAS  Google Scholar 

  • Kim YI, Fawaz K, Knox T, Lee YM, Norton R, Libby E et al. (2001) Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate Status among individuals ingesting physiologic quantities of folate. Cancer Epidemiol Biomarkers Prev 10(6): 715–719

    PubMed  CAS  Google Scholar 

  • Koutsos MI, Shiff SJ, Rigas B (1995) The effect of ursodeoxycholic and lithocholic acid on cell cycle and apoptosis in human colon adenocarcinoma cells. Gastroenterology 108: A492

    Google Scholar 

  • Kullmann F, Schlottmann K, Schölmerich J (1999) Bile acids and their role in colorectal Cancer. In: Schmiegel W, Schölmerich J (eds) Colorectal Cancer: molecular mechanisms, premalignant State and its prevention. Kluwer Academic Publishers, Dordrecht Boston London, pp 203–217

    Google Scholar 

  • Laird PW, Jaenisch R (1994) DNA methylation and Cancer. Hum Mol Genet 3:1487–1495

    PubMed  CAS  Google Scholar 

  • Lashner BA, Heidenreich PA, Su GL, Kane SV, Hanauer SB (1989) Effect of folate supplementation on the incidence of dysplasia and Cancer in chronic ulcerative Colitis. A case-control study. Gastroenterology 97(2): 255–259

    PubMed  CAS  Google Scholar 

  • Lashner BA (1993) Red blood cell folate is associated with the development of dysplasia and Cancer in ulcerative Colitis. J Cancer Res Clin Oncol 119(9): 549–554

    Article  PubMed  CAS  Google Scholar 

  • Lashner BA, Provencher KS, Seidner DL, Knesebeck A, Brzezinski A (1997) The effect of folic acid supplementation on the risk for Cancer or dysplasia in ulcerative Colitis. Gastroenterology 112(1): 29–32

    Article  PubMed  CAS  Google Scholar 

  • Meenan J, O’Hallinan E, Lynch S, Molloy A, McPartlan J, Scott J et al. (1996) Folate Status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects. Gut 38(3): 410–413

    Article  PubMed  CAS  Google Scholar 

  • Meenan J, O’Hallinan E, Scott J, Weir DG (1997) Epithelial cell folate depletion occurs in neoplastic but not adjacent normal colon mucosa. Gastroenterology 112(4): 1163–1168

    Article  PubMed  CAS  Google Scholar 

  • Meyer F, White E (1993) Alcohol and nutrients in relation to colon Cancer in middleaged adults. Am J Epidemiol 138(4): 225–236

    PubMed  CAS  Google Scholar 

  • Owen RW (1997) Faecal Steroids and colorectal carcinogenesis. Scand J Gastroenterol Suppl 222: 76–82

    PubMed  CAS  Google Scholar 

  • Paspatis GA, Kalafatis E, Oros L, Xourgias V, Koutsioumpa P, Karamanolis DG (1995) Folate Status and adenomatous colonic polyps. A colonoscopically controlled study. Dis Colon Rectum 38(1): 64–67

    Article  PubMed  CAS  Google Scholar 

  • Patel T, Bronk SF, Gores GJ (1994) Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rathepatocytes. J Clin Invest 94(6): 2183–2192

    Article  PubMed  CAS  Google Scholar 

  • Pohl C, Hombach A, Kruis W (2000) Chronic inflammatory bowel disease and Cancer. Hepatogastroenterology 47(31): 57–70

    PubMed  CAS  Google Scholar 

  • Rafter JJ, Eng VWS, Furrer R, Medline A, Bruce WR (1986) Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon. Gut 27:1320–1329

    Article  PubMed  CAS  Google Scholar 

  • Rampersaud GC, Kauwell GP, Hutson AD, Cerda JJ, Bailey LB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 72(4): 998–1003

    PubMed  CAS  Google Scholar 

  • Reddy BS, Wynder EL (1973) Large-bowel carcinogenesis: fecal constituents of populations with diverse incidence rates of colon Cancer. J Natl Cancer Inst 50(6): 1437–1442

    PubMed  CAS  Google Scholar 

  • Reddy BS, Wynder EL (1977) Metabolie epidemiology of colon Cancer. Fecal bile aeids and neutral sterols in colon Cancer patients and patients with adenomatous polyps. Cancer 39(6): 2533–2539

    Article  PubMed  CAS  Google Scholar 

  • Reddy BS, Engle A, Simi B, Goldman M (1992) Effect of dietary fiber on colonic bacterial enzymes and bile aeids in relation to colon Cancer. Gastroenterology 102:1475–1482

    PubMed  CAS  Google Scholar 

  • Rodrigues CMP, Fan G, Ma X, Kren BT, Steer CJ (1998) A novel role for ursodeoxyeholic acid inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 101: 2790–2799

    Article  PubMed  CAS  Google Scholar 

  • Ryan BM, Weir DG (2001) Relevance of folate metabolism in the pathogenesis of colorectal Cancer. J Lab Clin Med 138(3): 164–176

    Article  PubMed  CAS  Google Scholar 

  • Schölmerich J, Becher M-S, Schmidt K, Schubert R, Kremer B, Feldhaus S et al. (1984) Influence of hydroxylation and conjungation of bile salts on their membrane-damaging properties — studies on isolated hepatocytes and liquid membrane vesicles. Hepatology 4(4): 661–666.

    Article  PubMed  Google Scholar 

  • Shen L, Fang J, Qiu D, Zhang T, Yang J, Chen S et al. (1998) Correlation between DNA methylation and pathological changes in human hepatocellular Carcinoma. Hepatogastroenterology 45(23): 1753–1759

    PubMed  CAS  Google Scholar 

  • Shetty K, Rybicki L, Brzezinski A, Carey WD, Lashner BA (1999) The risk for Cancer or dysplasia in ulcerative Colitis patients with primary sclerosing Cholangitis. Am J Gastroenterol 94(6): 1643–1649

    Article  PubMed  CAS  Google Scholar 

  • Schlottman K, Wachs FP, Krieg RC, Kullmann F, Schölmerich J, Rogler G (2000) Characterization of bile salt-induced apoptosis in colon Cancer cell lines. Cancer Res 60(15): 4270–4276

    PubMed  CAS  Google Scholar 

  • Trock B, Lanza E, Greenwald P (1990) Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. J Natl Cancer Inst 82(8): 650–661

    Article  PubMed  CAS  Google Scholar 

  • Tung BY, Emond MJ, Haggitt RC, Bronner MP, Kimmey MB, Kowdley KV et al. (2001) Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative Colitis and primary sclerosing Cholangitis. Ann Intern Med 134(2): 89–95

    PubMed  CAS  Google Scholar 

  • Wainfan E, Dizik M, Stender M, Christman JK (1989) Rapid appearance of hypome-thylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets. Cancer Res 49(15): 4094–4097

    PubMed  CAS  Google Scholar 

  • Wolf JM, Rybicki L, Lashner BA (2001) Ursodeoxycholic acid is not chemopreventive for colorectal cancer in ulcerative Colitis patients with primary sclerosing Cholangitis. Gastroenterology 120[Suppl 1 ]: A447

    Google Scholar 

  • Wynder EL, Shigematsu T (1967) Environmental factors of cancer of the colon and rectum. Cancer 20:1520–1561

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Kullmann, F. (2003). Folsäure und Ursodesoxycholsäure. In: Dignass, A., Stein, J. (eds) Chronisch entzündliche Darmerkrankungen. Gastroenterologie Update, vol 2002. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-19025-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-19025-4_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-44152-6

  • Online ISBN: 978-3-642-19025-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics