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Biochemical Changes of Intestinal Epithelial Cells Induced by Cytostatic Agents in Rats

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Receptors and Other Targets for Toxic Substances

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 8))

Abstract

In the intestinal epithelium the rapidly proliferating crypt cells, the precursors of the mature enterocytes are extremely sensitive to the effects of cytostatic agents. The symptoms of intestinal impairment: nausea, vomiting, diarrhea, ulceration, are well known both in clinical practice and in experimental chemotherapy. To obtain information about the biochemical nature of these side effects, a study was performed by investigating the influence of clinically used alkylating hexitol derivatives, dianhydrogalactitol and diacetyl-dianhy-drogalactitol, on rat intestinal mucosa cells. The biochemical parameters were investigated in isolated intestinal mucosa cells. Cell proliferation was characterized by measuring the activity of thymidine kinase, while digestion was evaluated by assaying the alkaline phosphatase, sucrase and maltase activities localized in the brush border membrane of the villus cells. The dose response studies of the different enzyme activities indicated that inhibition in all cases was dose dependent. The nadir of the intestinal damage and the time of regeneration were influenced both by the dose and the dosage schedule of the drugs.

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References

  • Alpers DH, Kinzie JL (1973): Regulation of small intestinal protein metabolism. Gastroenterology 64, 471–496

    PubMed  CAS  Google Scholar 

  • Altenbrunn HJ, Georgi P, Berndt H, Bohn H, Pospisil Ch (1967): Die Prüfung der Fettresorption mit 131J-triolein bei Patienten mit malignen Tumoren nach Cyclophosphamid and Methotrexattherapie. In: Radioisotope in der Gastroenterologie (Hoffmann G. ed.) Schattauer Stuttgart

    Google Scholar 

  • Berndt H, Kutschke ID (1976): Der Einfluss der cytostatischen Chemotherapie mit Amethopterin auf die Thiamineversorgung Klin. Wschr. 16, 845–846

    Google Scholar 

  • Beró T, Mózsik Gy, Javor T (1976): D-xylose felszivódasanak vizsgalata combinalt cytostaticummal kezelt betegeken. Orv. Hetil. 117, 22–25

    PubMed  Google Scholar 

  • Bessey OA, Lowry OH, Brock MI (1965): Determination of alkaline phosphatase in serum with pnitrophenylphosphate. In: Methods of enzymatic analysis ( Bergmeyer H.U. ed.) pp 783–785 Verlag Chemie GMBH Weinheim, Academic Press New-York and London

    Google Scholar 

  • Caspary WF (1972): On the mechanism of D-xylose absorption from the intestine. Gastroenterology 63, 351–352

    Google Scholar 

  • Chiuten DF, Rozenzweig M, von Hoff DD, Muggia M (1981): Clinical trials with hexitol derivatives in the US. Cancer 47, 442–451

    Article  PubMed  CAS  Google Scholar 

  • Clarke RM (1970): Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat. J. Anat. 107, 519–529

    PubMed  CAS  Google Scholar 

  • Dahlqvist A (1968): Assay of intestinal disaccharidases. Anal. Biochem. 22, 99–107

    Article  PubMed  CAS  Google Scholar 

  • De Both NJ, Plaisier H (1974): The influence of changing cell kinetics on functional differentiation in the small intestine of the rat. A study of enzymes involved in carbohydrate metabolism. J. Histochem. Cytochem. 22, 352–360

    Article  PubMed  Google Scholar 

  • Ecknauer R, Rommel K (1978): Zytostatika and Dünndarm. Klin. Wschr. 56, 579–592

    Article  PubMed  CAS  Google Scholar 

  • Erdélyi-Tóth V, Kerpel-Fronius S, Kanyar B, Eckhardt S (1984): Lack of correlation between dose and plasma level in a phase I. trial with an alkylating agent diacetyldianhydrogalactitol (DADAG). Cancer. Chemother. Pharmacol. (Submitted for publication)

    Google Scholar 

  • Fromm H, Rodgers JB (1971): Effect of aminopterin on lipid absorption depression of lipid reesterifying enzymes. Amer. J. Physiol. 221, 998–1003

    PubMed  CAS  Google Scholar 

  • Hartree EF (1970): Determination of protein. A modification of the Lowry method that gives a linear photometric response. Anal. Biochem. 48, 422–427

    Article  Google Scholar 

  • Hartwich G (1974): Side effects of a cytostatic treatment on the gastrointestinal tract. Acta HepatoGastroenterol. 21, 89–92

    CAS  Google Scholar 

  • Herbst JJ, Hurwitz P, Sunshine P, Kretschmer N (1970): Effect of colchicine on intestinal disaccharidases correlation with biochemical aspects of cell renewal. J. Clin. Invest. 49, 530–536

    Article  PubMed  CAS  Google Scholar 

  • Heyman M, Desjeux JF, Grasset E, Dumontier AM, Lestradet H (1981): Relationship between transport of D-xylose and other monosaccharidases in jejunal mucosa of children. Gastroenterology 80, 758–762

    PubMed  CAS  Google Scholar 

  • Klemperer C, Haynes J (1968): Thymidine kinase in rat liver during development. Biochem. J. 108, 541–546

    PubMed  CAS  Google Scholar 

  • Kralovanszky J, Prajda N, Kerpel-Fronius S, Szentirmay Z (1981): Biological model system for investigating gastrointestinal side effects caused by cytostatic agents. In: Gastrointestinal Defence Mechanisms ( Mózsik Gy., Hänninen O., Javor T. eds.) pp 327–338 Pergamon Press London, Akadémiai Kiadó Budapest

    Google Scholar 

  • Mitchell EP, Schein PS (1982): Gastrointestinal Toxicity of Chemotherapeutic Agents Seminars in Oncology. 9, 52–64

    CAS  Google Scholar 

  • Németh L, Institóris L, Somfai S, Gal F, Pâlyi I, Sugar J, Csuka O, Szentirmay Z, Kellner B (1972): Pharmacologic and antitumor effect of 1,2:5,6 dianhydrogalactitol (NSC 132313) Cancer Chemother. Rep. 56, 593–602

    Google Scholar 

  • Ötvös L, Institóris L, Somfai S, Szabolcs A, Elekes I (1976): Dianhydrodulcitol derivative as pro-drugs. Vth Int. Symp. on Medicinal Chemistry Paris

    Google Scholar 

  • Parrilli G, Jaffaioli RV, Capuano G, Budillon G, Bianco AR (1982): Changes in intestinal permeability to lactulose induced by cytotoxic chemotherapy. Cancer Treatm. Rep. 66, 1435–1436

    CAS  Google Scholar 

  • Prajda N, Weber G (1975): Malignant transformation-linked imbalance: Decreased xanthine-oxidase activity in hepatomas. FEBS Lett. 59, 245–249

    Article  PubMed  CAS  Google Scholar 

  • Roche AC, Bognel JC, Bernier JJ (1970): Correlation between the histological changes and glucose intestinal absorption following a single dose of 5-Fluorouracil. Digestion 3, 195–212

    Article  PubMed  CAS  Google Scholar 

  • Silk, DB (1974): Peptide absorption in man. Gut 15, 494–501

    Article  PubMed  CAS  Google Scholar 

  • Sleisenger AH, Kim YS (1979): Protein digestion and absorption. New Engl. J. Med. 300, 659–663

    Article  PubMed  CAS  Google Scholar 

  • Somfai S, Gati E, Bence J, Gal F (1978): New derivatives of dianhydrogalactitol (NSC 132313) with significant antitumor activity. In: Current Chemotherapy ( Siegenthaler W., Lüthy R. eds.) Vol. II. pp. 1302–1303 Amer. Soc. Microbiol. Washington

    Google Scholar 

  • Weiser MM (1973): Intestinal epithelial cell surface membrane glycoprotein synthesis. J. Biol. Chem. 248, 2536–2541

    PubMed  CAS  Google Scholar 

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© 1985 Springer-Verlag

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Kralovánszky, J., Prajda, N. (1985). Biochemical Changes of Intestinal Epithelial Cells Induced by Cytostatic Agents in Rats. In: Chambers, P.L., Cholnoky, E., Chambers, C.M. (eds) Receptors and Other Targets for Toxic Substances. Archives of Toxicology, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69928-3_11

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  • DOI: https://doi.org/10.1007/978-3-642-69928-3_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-13670-5

  • Online ISBN: 978-3-642-69928-3

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