Subscribe to RSS
DOI: 10.1055/s-2000-10027
Aminosalizylate und Aspirin bei Kolonkarzinomen: vom Entzündungshemmer zum Tumorprophylaktikum?
Publication History
                     22.11.1999
                     
                     24.3.2000
                     
Publication Date:
31 December 2000 (online)

Zusammenfassung
Ziel dieser Arbeit ist es, einen Überblick zu geben über Antitumoreigenschaften von Medikamenten, die ursprünglich als Entzündungshemmer eingesetzt wurden, wie Aminosalizylate, Aspirin oder andere nichtsteroidale Antiphlogistika. Ausgehend von experimentellen und epidemiologischen Untersuchungen, die prophylaktische und/oder Tumorregressions/-suppressionseigenschaften belegen, werden spezifische antineoplastische Wirkungsweisen dargelegt wie die Hemmung Zyklooxygenase (COX)-abhängiger und -unabhängiger Schritte einschließlich der Rolle von Transkriptionsfaktoren wie NFkB in der Regulation des Zellzyklus. Darüber hinaus spielen weitere tumorhemmende Eigenschaften dieser Medikamente möglicherweise eine wichtige Rolle, wie die Induktion der Apoptose von Karzinomzellen und/oder Hemmung potenziell tumorrelevanter oxidativer DNA-Schäden. Basierend auf diesen Daten, wird die mögliche klinische Relevanz erörtert.
Aminosalicylates and aspirin for colonic cancer: From anti-inflammatory to antineoplastic drugs?
The aim of this article is to review potential antineoplastic properties of anti-inflammatory compounds commonly used in various inflammatory diseases such as aminosalicylates, aspirin and other nonsteroidal drugs. Starting from experimental and epidemiologic evidence showing prophylaxis and/or tumor regression/suppression, specific antineoplastic actions especially the inhibition of cyclooxygenase-(COX)dependent and COX-independent steps including the role of transscription factor (NFkB) in the cell cycle regulation are reviewed. In addition other mechanisms by which these drugs may exert antitumor effects, also may be important such as induction of apoptosis of cancer cells and/or inhibition of potentially carcinogenic oxidative DNA damage. Based on this knowledge potential clinical implications are discussed.
Schlüsselwörter
5-ASA - Aspirin - antitumoröse Effekte - Prostaglandin-/ Leukotriensynthesehemmung - COX-2-Hemmung - oxidative DNA-Schädigung - Apoptose
Key words
5-ASA - Aspirin - Antitumor Effects - Inhibition of Prostaglandins/Leukotriene Synthesis - COX-2 Inhibition - Oxidative DNA Damage - Apoptosis
Literatur
- 1 
            Boring C C, Squires T S, Tong T. 
            Cancer Statistics 1994. 
            Cancer J Clin. 
            1994; 
            44 
            7-26 
            
            Reference Ris Wihthout Link
- 2 
            Winawer S J, Zauber A G, Ho M N. et al .
            Prevention of colorectal cancer by colonoscopic polypectomy: The National Polyp Study
            Workgroup. 
            N Engl J Med. 
            1993; 
            329 
            1977-1981 
            
            Reference Ris Wihthout Link
- 3 Krebs in Deutschland, Häufigkeiten und Trends Arbeitsgemeinschaft Bevölkerungsbezogener
            Krebsregister in Deutschland. Saarbrücken; 1997 
            Reference Ris Wihthout Link
- 4 
            Thun M J. 
            NSAID use and decreased risk of gastrointestinal cancers. 
            Gastroenterol Clin North Am. 
            1996; 
            25 
            333-34 
            
            Reference Ris Wihthout Link
- 5 
            Shiff S J, Rigas B. 
            Nonsteroidal anti-inflammatory drugs and colorectal cancer: Evolving concepts of their
            chemopreventive actions. 
            Gastroenterology. 
            1997; 
            113 
            1992-1998 
            
            Reference Ris Wihthout Link
- 6 
            Klampfer L, Cammenga J, Wisniewski H, Nimer S D. 
            Sodium salicylate activates caspases and induces apoptosis of myeloid cell lines. 
            Blood. 
            1999; 
            93 
            2386-2394 
            
            Reference Ris Wihthout Link
- 7 
            Reinacker-Schick A, Seidensticker F, Petrasch S, Philippou S, Schmiegel W. 
            Mesalazine induces apoptosis and decreases proliferation in normal epithelial cells
            in patients with sporadic colorectal polyps. 
            Gastroenterology. 
            1998; 
            114 
            A 666 
            
            Reference Ris Wihthout Link
- 8 
            Reiser M, Schmiegel W. 
            Doppelblinde, multizentrische, placebokontrollierte Studie zur Prävention kolorektaler
            Polypen durch 5-Aminosalizylsäure nach Polypektomie (German 5-ASA-Polyp-Prevention
            Study) (GAPPS) (SAG-6). 
            Z Gastroenterol. 
            1999; 
            12 
            XXIII 
            
            Reference Ris Wihthout Link
- 9 
            Bedi A, Pasricha P J, Akhtar A J. et al .
            Inhibition of apoptosis during development of colorectal cancer. 
            Cancer Res. 
            1995; 
            55 
            1811-1816 
            
            Reference Ris Wihthout Link
- 10 
            Giardello F M, Offerhaus G JA, Du B ois RN. 
            Role of nonsteroidal drugs in colon cancer prevention. 
            Eur J Cancer. 
            1995; 
            31A 
            1071-1076 
            
            Reference Ris Wihthout Link
- 11 
            Alexandrov K, Rojas M, Kadlubar F F, Lang N P, Bartsch H. 
            Evidence of anti (a) pyrene diolepoxide-DNA adduct formation in human colonic mucosa. 
            Carcinogenesis. 
            1996; 
            17 
            2081-2083 
            
            Reference Ris Wihthout Link
- 12 
            Bartsch H. 
            Etheno-DNA base adducts as tools in human cancer etiology and chemoprevention. 
            Eur J Cancer Prevention. 
            1997; 
            6 
            529-534 
            
            Reference Ris Wihthout Link
- 13 
            Pollard M, Luckert P H. 
            Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. 
            Cancer Treat Rep. 
            1980; 
            64 
            1323-1327 
            
            Reference Ris Wihthout Link
- 14 
            Moorghen M, Ince P, Finney K J. et al .
            A protective effect of sulindac against chemically-induced primary colonic tumors
            in mice. 
            J Pathol. 
            1988; 
            156 
            341-347 
            
            Reference Ris Wihthout Link
- 15 
            Norisarou T, Satoh M, Nano M, Takahashi T. 
            Inhibition of initiation and promotion by N-methyl-nitroso urea-induced colon carcinogenesis
            in rats by non steroid anti-inflammatory drug indomethacin. 
            Carcinogenesis. 
            1982; 
            4 
            1225-1227 
            
            Reference Ris Wihthout Link
- 16 
            Pollard M, Ludkert P H, Schmid M A. 
            The suppressive effect of piroxicam on autochtonous intestinal tumors in the rat. 
            Cancer Lett. 
            1983; 
            21 
            57-61 
            
            Reference Ris Wihthout Link
- 17 
            Reddy B S, Rao C V, Rivenson A, Kelloff G. 
            Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344
            rats. 
            Carcinogenesis. 
            1993; 
            14 
            1493-1497 
            
            Reference Ris Wihthout Link
- 18 
            Reddy B S, Maruyama H, Kelloff G. 
            Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal
            anti-inflammatory drug during different stages of rat colon tumor development. 
            Cancer Res. 
            1987; 
            47 
            5340-5346 
            
            Reference Ris Wihthout Link
- 19 
            Jacoby R F, Marshall D J, Newton M A. et al .
            Chemoprevention of spontaneous intestinal adenomas in the APC Min mouse model by the
            non steroidal anti-inflammatory drug piroxicam. 
            Cancer Res. 
            1996; 
            56 
            710-714 
            
            Reference Ris Wihthout Link
- 20 
            Boolbol S K, Dannenberg A J, Chadburn A. et al .
            Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine
            model of familial adenomatous polyposis. 
            Cancer Res. 
            1996; 
            56 
            2556-2560 
            
            Reference Ris Wihthout Link
- 21 
            Beazer-Barclay Y, Levy D B, Moser A R. et al .
            Sulindac suppresses tumorigenesis in the Min mouse. 
            Carcinogenesis. 
            1996; 
            17 
            1757-1760 
            
            Reference Ris Wihthout Link
- 22 
            Powell S M, Ziliz N, Beaser-Barklay Y. et al .
            APC mutations occur early during colorectal tumorigenesis. 
            Nature. 
            1992; 
            359 
            235-237 
            
            Reference Ris Wihthout Link
- 23 
            Kinzler K W, Vogelstein B. 
            Lessons from hereditary colorectal cancer. 
            Cell. 
            1996; 
            87 
            159-170 
            
            Reference Ris Wihthout Link
- 24 
            Waddell W R, Loughry R W. 
            Sulindac for polyposis of the colon.  
            J Surg Oncol. 
            1983; 
            24 
            83-87 
            
            Reference Ris Wihthout Link
- 25 
            Barnes C J, Lee M. 
            Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli
            Min mouse model with aspirin. 
            Gastroenterology. 
            1998; 
            114 
            873-877 
            
            Reference Ris Wihthout Link
- 26 
            MacGregor D J, Kom Y S, Siddiki B B. et al .
            Induction of colon cancer cell apoptosis in vitro and inhibition of intestinal tumor
            formation in Min/+ mice by balsalazide and metabolites. 
            Gastroenterology. 
            1996; 
            110 
            A553 
            
            Reference Ris Wihthout Link
- 27 
            Ritland S R, Leigthon I A, Hirsch R E. et al .
            Evaluation of 5-aminosalicylic acid (5-ASA) for cancer prevention: Lack of efficacy
            against nascent adenomatous polyps in the APC (Min) mouse. 
            Clin Cancer Res. 
            1999; 
            5 
            855-863 
            
            Reference Ris Wihthout Link
- 28 
            Ekbom A, Helmick C, Zack M, Adami H O. 
            Ulcerative colitis and colorectal cancer. 
            N Engl J Med. 
            1990; 
            323 
            1228-1233 
            
            Reference Ris Wihthout Link
- 29 
            Isomäki H A, Hakulinen T, Joutsenlahti U. 
            Excess risk of lymphomas, leukemia and yeloma in patients with rheumatoid arthritis. 
            J Chron Dis. 
            1978; 
            31 
            691-696 
            
            Reference Ris Wihthout Link
- 30 
            Rosenberg L, Palmer J R, Zauber A G. et al .
            A hypothesis: Non-steroidal anti-inflammatory drugs reduce the incidence of large-bowel
            cancer. 
            J Natl Cancer Inst. 
            1991; 
            83 
            355-358 
            
            Reference Ris Wihthout Link
- 31 
            Peleg I I, Maibach H T, Brown S H, Wilcox C M. 
            Aspirin and nonstoidal anti-inflammatory drug use and the risk of subsequent colorectal
            cancer. 
            Arch Intem Med. 
            1994; 
            154 
            394-399 
            
            Reference Ris Wihthout Link
- 32 
            Schreinemachers D M, Eversen R B. 
            Aspirin use and lung, colon and breast cancer incidence in a prospective study. 
            Epidemiology. 
            1994; 
            5 
            138-146 
            
            Reference Ris Wihthout Link
- 33 
            Thun M J, Namboodiri M M, Calle E E, Flanders W D, Heath C W. 
            Aspirin use and reduced risk of fatal cancer. 
            N Engl J Med. 
            1991; 
            325 
            1593-1596 
            
            Reference Ris Wihthout Link
- 34 
            Thun M J, Calle E E, Namboodiri M M. et al .
            Risk factors for fatal colonic cancer in a large prospective study. 
            J Natl Cancer Inst. 
            1992; 
            84 
            1491-1500 
            
            Reference Ris Wihthout Link
- 35 
            Thun M J, Namboodiri M M, Calle E E, Flanders D W, Heath C W. 
            Aspirin use and risk of fatal cancer. 
            Cancer Res. 
            1993; 
            53 
            1322-1327 
            
            Reference Ris Wihthout Link
- 36 
            Paganini H ill A, Chao A, Ross K K, Henderson B E. 
            Aspirin use and chronic diseases: A cohort study of the elderly. 
            BMJ. 
            1989; 
            299 
            1247-1250 
            
            Reference Ris Wihthout Link
- 37 
            Paganini Hill A. 
            Aspirin and colorectal cancer: The Leisure World Cohort revisited. 
            Prev. Medicine. 
            1995; 
            24 
            113-115 
            
            Reference Ris Wihthout Link
- 38 
            Gann P H, Manson J E, Glynn J. et al .
            Low dose aspirin and incidence of colorectal tumors in a randomized trial. 
            J Natl Cancer Inst. 
            1993; 
            85 
            1220-1224 
            
            Reference Ris Wihthout Link
- 39 
            Stürmer T, Glynn R J, Lee I M. et al .
            Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians Health
            Study. 
            Ann Intern Med. 
            1998; 
            128 
            713-720 
            
            Reference Ris Wihthout Link
- 40 
            Smalley W, Rav W A, Daugherty J. 
            Use of nonsteroidal antiinflammatory drugs and incidence of colorectal cancer: a population-based
            study. 
            Arch. Int Med. 
            1999; 
            159 
            161-164 
            
            Reference Ris Wihthout Link
- 41 
            Giardello F M, Hamilton S R, Brush A J. et al .
            Treatment of colonic and rectal adenomatosis polyposis. 
            N Engl J Med. 
            1993; 
            328 
            1313-1316 
            
            Reference Ris Wihthout Link
- 42 
            Nugent K P, Farmer K, Spiegelman A D, Williams C B, Phillips R K. 
            Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis
            and cell proliferation in patients with familial adenomatous polyposis. 
            Br J Sury. 
            1993; 
            80 
            1618-1619 
            
            Reference Ris Wihthout Link
- 43 
            Keller J J, Ofterhaus G JA, Polak M. et al .
            Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with
            sulindac. 
            Gut. 
            1999; 
            45 
            822-828 
            
            Reference Ris Wihthout Link
- 44 
            Bachwich D R, Lichtenstein G R, Traber P G. 
            Cancer in inflammatory bowel disease. 
            Gastroenterol Clin North Am. 
            1994; 
            78 
            1399-1412 
            
            Reference Ris Wihthout Link
- 45 
            Kornfeld D. 
            Sulfasalazine use as a preventive factor for colorectal cancer in ulcerative colitis
            patients - a review. 
            Inflamm Bowel Dis. 
            1996; 
            2 
            276-278 
            
            Reference Ris Wihthout Link
- 46 
            Pinczowski D, Ekbom A, Baron J, Yuen J, Adami H O. 
            Risk factors for colorectal cancer in patients with ulcerative colitis: A case-control
            study. 
            Gastroenterology. 
            1994; 
            107 
            117-120 
            
            Reference Ris Wihthout Link
- 47 
            Thompson C B. 
            Apoptosis in the pathogenesis and treatment of disease. 
            Science. 
            1995; 
            267 
            1456-1462 
            
            Reference Ris Wihthout Link
- 48 
            Shiff S J, Qiao L, Tsai L -L, Rigas B. 
            Sulindac-sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle
            quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells.  
            J Clin Invest. 
            1995; 
            96 
            491-503 
            
            Reference Ris Wihthout Link
- 49 
            Shiff S j, Koutsos M J, Qiao L, Rigas B. 
            Nonsteroidal anti-inflammatory drugs inhibit the proliferation of colon adenocarcinoma
            cells: Effects on cell cycle and apoptosis. 
            Exp Cell Res. 
            1996; 
            222 
            179-188 
            
            Reference Ris Wihthout Link
- 50 
            Goldberg Y, Nassif I I, Pittas A. et al .
            The antiproliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer
            cells: Alterations in tumor suppressor and cell cycle regulatory proteins. 
            Oncogene. 
            1996; 
            12 
            893-901 
            
            Reference Ris Wihthout Link
- 51 
            Qiao L, Hanif R, Sphicas E, Shiff S J, Rigas B. 
            Effect of aspirin on induction of apoptosis in HT-29 human colon adenocarcinoma cells. 
            Biochem Pharmacol. 
            1998; 
            55 
            53-64 
            
            Reference Ris Wihthout Link
- 52 
            Qiao L, Shiff S J, Rigas B. 
            Sulindac sulfide inhibits the proliferation of colon cancer cells: diminished expression
            of the proliferation markers PCNA and Ki-67. 
            Cancer Lett. 
            1997; 
            115 
            229-234 
            
            Reference Ris Wihthout Link
- 53 
            Williams C W, Du B ois RN. 
            Prostaglandin endoperoxide synthetase: Why two isoforms?. 
            Am J Physiol. 
            1996; 
            270 
            G 393-G400 
            
            Reference Ris Wihthout Link
- 54 
            Bayer B M, Beaven M A. 
            Evidence that indomethacine reversibly inhibits cell growth in the G1 phase of the
            cell cycle. 
            Biochem Pharmacol. 
            1997; 
            28 
            441-443 
            
            Reference Ris Wihthout Link
- 55 
            Eberhart C E, Dubois R N. 
            Eicosanoids and the gastrointestinal tract. 
            Gastroenterology. 
            1995; 
            109 
            285-301 
            
            Reference Ris Wihthout Link
- 56 
            Marnett L J. 
            Aspirin and the potential role of prostaglandins in colon cancer. 
            Cancer Res. 
            1992; 
            52 
            5575-5589 
            
            Reference Ris Wihthout Link
- 57 
            Kargman S, O’Neil G, Vickers P. et al .
            Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. 
            Cancer Res. 
            1995; 
            55 
            2556-2559 
            
            Reference Ris Wihthout Link
- 58 
            Tsujii M, Kawano S, DuBois R N. 
            Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing
            prostaglandin endoperoxide synthase 2. 
            Cell. 
            1995; 
            83 
            493-501 
            
            Reference Ris Wihthout Link
- 59 
            Oshima M, Dichuk J E, Kargman S L. et al .
            Suppression of intestinal polyposis in APC(716 knockout mice by inhibition of cyclooxygenase-2
            (COX-2). 
            Cell. 
            1996; 
            87 
            803-809 
            
            Reference Ris Wihthout Link
- 60 
            Singh J, Hamid R, Reddy B S. 
            Dietary fat and colon cancer. Modulation of cyclooxygenase-2 by types and amount of
            dietary fat during the postinitiation stage of colon carcinogenesis. 
            Cancer Res. 
            1997; 
            57 
            3465-3470 
            
            Reference Ris Wihthout Link
- 61 
            Singer I I, Kawka D W, Schloemann S. et al .
            Cyclooxygenase-2 is induced in colonic epithelial cells in inflammatory bowel disease. 
            Gastroenterology. 
            1998; 
            115 
            297-306 
            
            Reference Ris Wihthout Link
- 62 
            Hanif R, Pittas A, Feng Y. et al .
            Effect of nonsteroidal anti-inflammatory drugs on proliferation and on induction of
            apoptosis in colon cancer cells by a prostaglandin-independent pathway. 
            Biochem Pharmacol. 
            1996; 
            52 
            237-245 
            
            Reference Ris Wihthout Link
- 63 
            Piazza G A, Albert D S, Hixon L J. et al .
            Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without
            reducing prostaglandin levels. 
            Cancer Res. 
            1997; 
            75 
            2909-2915 
            
            Reference Ris Wihthout Link
- 64 
            Elder D JE, Hague A, Hicks D J, Paraskeva C. 
            Differential growth inhibition by the aspirin metabolite salicylate in human colorectal
            tumor cell lines: Enhanced apoptosis in carcinoma and in vitro-transformed adenoma
            relative to adenoma cell lines. 
            Cancer Res. 
            1996; 
            56 
            2273-2276 
            
            Reference Ris Wihthout Link
- 65 
            Kopp E, Ghosh S. 
            Inhibition of NFkB by sodium salicylate and aspirin. 
            Science. 
            1994; 
            265 
            956-959 
            
            Reference Ris Wihthout Link
- 66 
            Kaiser G C, Yan F, Polk D B. 
            Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kB activation
            in mouse colonocytes. 
            Gastroenterology. 
            1999; 
            116 
            602-609 
            
            Reference Ris Wihthout Link
- 67 
            Hinz M, Krappmann D, Eichten A. et al .
            NF-kB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase
            transition. 
            Mol Cell Biol. 
            1999; 
            19 
            2690-2698 
            
            Reference Ris Wihthout Link
- 68 
            Yin M -J, Yamamoto Y, Gaynor R B. 
            The anti-inflammatory agents aspirin and salicylate inhibit the activity of IkB kinase-ß. 
            Nature. 
            1998; 
            396 
            77-80 
            
            Reference Ris Wihthout Link
- 69 
            Schwenger P, Bellosta P, Vietor I. et al .
            Sodium salicylate induces apoptosis via p38 mitogen-activated protein kinase but inhibits
            tumor necrosis factor-induced c-Jun N-terminal kinase/stress-activated protein kinase
            activation. 
            Proc Natl Acad Sci USA. 
            1997; 
            94 
            2869-2873 
            
            Reference Ris Wihthout Link
- 70 
            Chan T A, Morin P J, Vogelstein B, Kinzler K W. 
            Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis. 
            Proc Natl Acad Sci USA. 
            1998; 
            95 
            681-686 
            
            Reference Ris Wihthout Link
- 71 
            Hall P A, Coates P J, Ansari B, Hopwood D. 
            Regulation of cell number in the mammalian gastrointestinal tract: The importance
            of apoptosis. 
            J Cell Sci. 
            1994; 
            107 
            3569-3577 
            
            Reference Ris Wihthout Link
- 72 
            Bedi A, Pasricha P J, Akhtar A J, Barber J P. et al .
            Inhibition of apoptosis during development of colorectal cancer. 
            Cancer Res. 
            1995; 
            55 
            1811-1816 
            
            Reference Ris Wihthout Link
- 73 
            Wang C -Y, Mayo M W, Korneluk R G, Goeddel D V, Baldwin A S. 
            NF-kB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress
            caspase-8 activation. 
            Science. 
            1998; 
            281 
            1680-1683 
            
            Reference Ris Wihthout Link
- 74 
            Piazza G A, Rahm A LK, Krutzsch M. et al .
            Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing
            apoptosis. 
            Cancer Res. 
            1995; 
            55 
            3110-3116 
            
            Reference Ris Wihthout Link
- 75 
            Sheng H, Shao J, Morrow J D, Beauchamp R D, DuBois R N. 
            Modulation of apoptosis and bcl-2 expression by prostaglandin E2 in human colon cancer
            cells. 
            Cancer Res. 
            1998; 
            58 
            362-366 
            
            Reference Ris Wihthout Link
- 76 
            Tillmann T, Hombach A, Diehl V. et al .
            Inhibition der Expression von bcl-2 als möglicher Wirkungsmechanismus der chemoprotektiven
            Wirkung von Salizylsäure gegen Kolonkarzinome.  
            Z Gastroenterol. 
            1998; 
            36 
            A706 
            
            Reference Ris Wihthout Link
- 77 
            Sinicrope F A, Ruan S B, Cleary K R. et al .
            bcl-2 and p53 oncoprotein expression during colorectal carcinogenesis. 
            Cancer Res. 
            1995; 
            55 
            237-241 
            
            Reference Ris Wihthout Link
- 78 
            Baretton G D, Diebold J, Chrstiforis G. et al .
            Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomes and carcinomas. 
            Cancer. 
            1996; 
            77 
            255-264 
            
            Reference Ris Wihthout Link
- 79 
            Winde G, Schmid K W, Brandt B, Müller O, Osswald H. 
            Clinical and genomic influence of sulindac on rectal mucosa in familial adenomatous
            polyposis. 
            Dis Colon Rectum. 
            1997; 
            40 
            1156-1169 
            
            Reference Ris Wihthout Link
- 80 
            Wu G D. 
            A nuclear receptor to prevent colon cancer. 
            N Engl J Med. 
            2000; 
            342 
            651-653 
            
            Reference Ris Wihthout Link
- 81 
            Allgayer H, Stenson W F. 
            A comparison of effects of sulfasalazine and its metabolites on the metabolism of
            endogenous vs. exogenous arachidonic acid. 
            Immunopharmacology. 
            1988; 
            15 
            39-46 
            
            Reference Ris Wihthout Link
- 82 
            Dittmann K H, Mayer C X, Rodemann H P, Perides P E, Denzlinger C. 
            MK 886, a leukotriene biosynthesis inhibitor, induces antiproliferative effects and
            apotposis in HL-60 cells. 
            Leukemia Research. 
            1998; 
            52 
            49-53 
            
            Reference Ris Wihthout Link
- 83 
            Loft S, Poulsen H E. 
            Cancer risk and oxidative DNA damage in man. 
            J Mol Med. 
            1996; 
            74 
            297-312 
            
            Reference Ris Wihthout Link
- 84 
            Cheng K C, Cahill D S, Kasai H, Nishimura S, Loeb L A. 
            8-Hydroxyguanine, an abundant form of oxidative DNA damage causes G-T and A-C substitutions. 
            J Biol Chem. 
            1992; 
            267 
            166-172 
            
            Reference Ris Wihthout Link
- 85 
            Schmutte C, Yang A S, Beart R W, Jones P A. 
            Base excision repair of U:G mismatches at mutational hotspot in the p53 gene is more
            efficient than base excision repair of T:G mismatches in extracts of human colon tumors. 
            Cancer Res. 
            1995; 
            55 
            3742-3746 
            
            Reference Ris Wihthout Link
- 86 
            Malins D C, Haimanot R. 
            Major alterations in the nucleotide structure of DNA in cancer of the female breast. 
            Cancer Res. 
            1991; 
            51 
            5430-5432 
            
            Reference Ris Wihthout Link
- 87 
            Farinati F, Cardin R, Rugge M. et al .
            Oxidative DNA damage accumulation in gastric carcinogenesis. 
            Gut. 
            1998; 
            42 
            351-356 
            
            Reference Ris Wihthout Link
- 88 
            Pool-Zobel B L, Collins A K, Rechkammer G. 
            Levels of endogenous DNA damage and oxidized DNA bases in colon cells derived from
            biopsies 50 non colon cancer patients. 
            Proc Annu Meet Am Ass Cancer Res. 
            1997; 
            38 
            A300 
            
            Reference Ris Wihthout Link
- 89 
            Lih-Brody L, Powell S R, Collier K P. et al .
            Increased oxidative stress and decreased antioxidative defenses in mucosa of inflammatory
            bowel disease. 
            Dig Dis Sci. 
            1996; 
            41 
            2078-2086 
            
            Reference Ris Wihthout Link
- 90 
            Allgayer H, Höfer P, Schmidt M. et al .
            Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct
            evaluation with electron spin resonance spectroscopy. 
            Biochem Pharmacol. 
            1992; 
            43 
            259-262 
            
            Reference Ris Wihthout Link
- 91 
            Allgayer H, Such P, Klotz P, Fischer C, Kruis W. 
            Formation and inhibition of deoxyribose radicals: Potential disease mechanisms and
            modes of action of aminosalicylates in inflammatory bowel disease. 
            Magn Reson Med. 
            1995; 
            6 
            237-239 
            
            Reference Ris Wihthout Link
- 92 
            Allgayer H, Kolb M, Stuber V, Kruis W. 
            Modulation of base hydroxylation by bile acids and salicylates in a model of human
            colonic mucosal DNA: Putative implications in colonic cancer. 
            Dig Dis Sci. 
            1999; 
            44 
            761-767 
            
            Reference Ris Wihthout Link
- 93 
            Rainford K D. 
            The effects of aspirin and other non-steroid antiinflammatory analgesic drugs an gastrointestinal
            mucus glycoprotein biosynthesis in vivo: Relationship to ulcerogenic actions. 
            Biochem Pharmacol. 
            1978; 
            27 
            877-885 
            
            Reference Ris Wihthout Link
- 94 
            Lauritsen K, Hansen J, Ryde M, Rask-Madsen J. 
            Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers
            and patients with ulcerative colitis. 
            Gastroenterology. 
            1984; 
            86 
            1496-1500 
            
            Reference Ris Wihthout Link
- 95 
            Nair J, Vaca E, Velic J. et al .
            High dietary omega 6-polyursattenated fatty acids drastically increase the formation
            of etheno-DNA base adducts in white blood cells of female subjects. 
            Cancer Epidemiol Biomarkers Prev. 
            1997; 
            6 
            597-601 
            
            Reference Ris Wihthout Link
- 96 
            Gupta R A, DuBois R N. 
            Aspirin, NSAIDs and colon cancer prevention: Mechanisms?. 
            Gastroenterology. 
            1998; 
            114 
            1095-1109 
            
            Reference Ris Wihthout Link
- 97 
            Kontsos M J, Shift S J, Rigas B. 
            Can non-steroidal anti-inflammatory drugs be recommended to prevent colon cancer in
            high risk elderly patients?. 
            Drugs Aging. 
            1995; 
            6 
            421-425 
            
            Reference Ris Wihthout Link
- 98 
            Greenberg E R, Baron J A. 
            Aspirin and other non steroid anti-inflammatory drugs as cancer-preventive agents. 
            IAR Sci Publ. 
            1996; 
            139 
            91-96 
            
            Reference Ris Wihthout Link
- 99 
            Langman M, Boyle P. 
            Chemoprevention of colorectal cancer. 
            Gut. 
            1998; 
            43 
            585-588 
            
            Reference Ris Wihthout Link
- 100 
            Walker A M, Snzeke P, Bianchi L A. et al .
            5-Aminosalicylates, sulfasalazine, steroid use and complications in patients with
            ulcerative colitis. 
            Am J Gastroenterol. 
            1997; 
            92 
            816-820 
            
            Reference Ris Wihthout Link
- 101 
            Steinbach G, Lynch P M, Phillips RK S. et al .
            The effect of celecobix, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. 
            N Engl J Med. 
            2000; 
            342 
            1946-1952 
            
            Reference Ris Wihthout Link
Anschrift für die Verfasser:
Prof. Dr. H Allgayer
         Rehaklinik Ob der Tauber der LVA Württemberg
         
         Bismarckstraße 31
         
         97980 Bad Mergentheim
         
         Fax: 07931 541 6001
         
         
 
     
      
    