Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-20T05:47:59.277Z Has data issue: false hasContentIssue false

Mechanisms and anticarcinogenic effects of diet-related apoptosis in the intestinal mucosa

Published online by Cambridge University Press:  14 December 2007

Ian T. Johnson*
Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Corresponding author: Professor Ian T. Johnson, fax +44 1603 255267, email
Rights & Permissions [Opens in a new window]


Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

There is now ample epidemiological evidence to show that the wide international variations in the incidence of both adenomatous polyps and colo-rectal cancer are linked to diet, but the mechanisms through which particular dietary constituents influence the onset of neoplasia are poorly understood. The crypt epithelial cells of the human gastrointestinal mucosa are amongst the most rapidly proliferating tissues in the body, and those of the colorectum are particularly vulnerable to neoplasia. Within the crypt, continuous division of basally localized stem cells gives rise to daughter cells that may divide once or twice again, before differentiating and migrating to the mucosal surface. The majority of nascent crypt epithelial cells differentiate, become senescent and are shed into the gut lumen, but a small proportion die by apoptosis soon after cell division. Various lines of evidence suggest that these pathways of programmed cell death provide a protective mechanism against induction of neoplasia by removing genetically damaged stem cells before they can divide further and give rise to precancerous lesions. There is evidence that the short-chain fatty acid butyrate and several different classes of food constituents, including some polyunsaturated fatty acids, flavonoids and glucosinolate breakdown products, can regulate the processes of cell proliferation and death in vitro, and in colorectal crypts in vivo. All three classes of food components suppress the emergence of aberrant crypt foci in animal models of carcinogenesis. The cellular mechanisms underlying these phenomena, and their possible significance for human health, are discussed.

Research Article
Copyright © CABI Publishing 2001


Adams, JM & Cory, S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281, 13221326.CrossRefGoogle ScholarPubMed
Adamson, RH, Thorgeirsson, UP & Sugimura, T (1996) Extrapolation of heterocyclic amine carcinogenesis data from rodents and nonhuman primates to humans. Archives of Toxicology 71, Suppl. 18, 303318.CrossRefGoogle Scholar
Afford, S & Randhawa, S (2000) Apoptosis. Journal of Clinical Pathology: Molecular Pathology 53, 5563.Google ScholarPubMed
Ames, B & Swirsky Gold, L (1991) Mitogenesis, mutagenesis, and animal cancer tests. Chemically induced cell proliferation: implications for risk assessment. Progress in Clinical and Biological Research 369, 120.Google Scholar
Anti, MArmelao, FMarra, GPercesepe, ABartoli, GMPalozza, PParrella, PCanetta, CGentiloni, NDe Vitis, I and Gasbarrini, G (1994) Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107, 17091718.CrossRefGoogle ScholarPubMed
Antunes, F & Cadenas, E (2001) Cellular titration of apoptosis with steady-state concentrations of H2O2: submicromolar levels of H2O2 induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free Radicals in Biology and Medicine 30, 10081018.CrossRefGoogle ScholarPubMed
Augeron, C & Laboisse, C (1984) Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Research 44, 39613969.Google Scholar
Avivi-Green, CMadar, Z & Schwartz, B (2000 a) Pectin-enriched diet affects distribution and expression of apoptosis-cascade proteins in colonic crypts of dimethylhydrazine-treated rats. International Journal of Molecular Medicine 6, 689698.Google ScholarPubMed
Avivi-Green, CPolak-Charcon, SMadar, Z & Schwartz, B (2000 b) Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition. Oncology Research 12, 8395.CrossRefGoogle ScholarPubMed
Bach, SPRenehan, AG & Potten, CS (2000) Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis 21, 469476.CrossRefGoogle ScholarPubMed
Barnard, JA & Warwick, G (1993) Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. Cell Growth and Differentiation 4, 495501.Google ScholarPubMed
Barthold, SW & Beck, D (1980) Modification of early dimethylhydrazine carcinogenesis by colonic mucosal hyper- plasia. Cancer Research 40, 44514455.Google Scholar
Begin, MEDas, UNElls, G & Horrobin, DF (1985) Selective killing of human cancer cells by polyunsaturated fatty acids. Prostaglandins and Leukotrienes in Medicine 19, 177186.CrossRefGoogle ScholarPubMed
Begin, MEElls, GDas, UN & Horrobin, DF (1986) Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. Journal of the National Cancer Institute 77, 10531062.Google ScholarPubMed
Bellamy, COMalcomson, RDHarrison, DJ & Wyllie, AH (1995) Cell death in health and disease: the biology and regulation of apoptosis. Seminars in Cancer Biology 6, 316.CrossRefGoogle ScholarPubMed
Bielas, JH & Heddle, JA (2000) Proliferation is necessary for both repair and mutation in transgenic mouse cells. Proceedings of the National Academy of Sciences USA 97, 1139111396.CrossRefGoogle ScholarPubMed
Bingham, SAPignatelli, BPollock, JRAEllul, AMalaveille, CGross, GRunswick, SCummings, JH and O'Neill, IK (1996) Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer? Carcinogenesis 17, 515523.CrossRefGoogle ScholarPubMed
Bodmer, WF (1994) Cancer genetics. British Medical Bulletin 50, 517526.CrossRefGoogle ScholarPubMed
Bodmer, WF (1999) 1998 Runme Shaw Memorial Lecture: Somatic evolution of cancer. Annals of the Academy of Medicine of Singapore 28, 323329.Google ScholarPubMed
Boffa, LCLupton, JRMariani, MRCeppi, MNewmark, HLScalmati, A & Lipkin, M (1992) Modulation of colonic epithelial cell proliferation histone acetylation and luminal short chain fatty acids by variation of dietary fiber (wheat bran) in rats. Cancer Research 52, 59065912.Google ScholarPubMed
Bonithon-Kopp, CKronborg, OGiacosa, ARath, U & Faivre, J (2000) Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet 356, 13001306.CrossRefGoogle ScholarPubMed
Bracey, TSMiller, JCPreece, A & Paraskeva, C (1995) Gamma-radiation-induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53. Oncogene 10, 23912396.Google ScholarPubMed
Brown, LMSwanson, CAGridley, GSwanson, GMSchoenberg, JBGreenberg, RSSilverman, DTPottern, LMHayes, RBSchwartz, AGLiff, JMFraumeni, JF & Hoover, RN (1995) Adenocarcinoma of the esophagus: role of obesity and diet. Journal of the National Cancer Institute 87, 104109.CrossRefGoogle ScholarPubMed
Caderni, GLuceri, CDe Filippo, CSalvadori, MGiannini, ATessitore, L & Dolara, P (2001) Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced intestinal carcinogenesis in F344 rats. Carcinogenesis 22, 525527.CrossRefGoogle Scholar
Caderni, GLuceri, CLancioni, LTessitore, L & Dolara, P (1998) Slow-release pellets of sodium butyrate increase apoptosis in the colon of rats treated with azoxymethane without affecting aberrant crypt foci and colonic proliferation. Nutrition and Cancer 30, 175181.CrossRefGoogle ScholarPubMed
Cai, WBRoberts, SA & Potten, CS (1997) The number of clonogenic cells in crypts in three regions of murine large intestine. International Journal of Radiation Biology 71, 573579.Google ScholarPubMed
Chai, FEvdokiou, AYoung, GP & Zalewski, PD (2000) Involvement of p21(Waf1/Cip1) and its cleavage by DEVD- caspase during apoptosis of colorectal cancer cells induced by butyrate. Carcinogenesis 21, 714.CrossRefGoogle ScholarPubMed
Chan, TAMorin, PJVogelstein, B & Kinzler, KW (1998) Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis. Proceedings of the National Academy of Sciences USA 95, 681686.CrossRefGoogle ScholarPubMed
Chang, WChapkin, RS & Lupton, JR (1997) Predictive value of proliferation differentiation and apoptosis as intermediate markers for colon tumorigenesis. Carcinogenesis 18, 721730.CrossRefGoogle ScholarPubMed
Chapkin, RSFan, Y & Lupton, JR (2000) Effect of diet on colonic-programmed cell death: molecular mechanism of action. Toxicology Letters 112, 411414.CrossRefGoogle ScholarPubMed
Clarke, RGLund, EKLatham, PPinder, AC & Johnson, IT (1999) Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29. Lipids 34, 12871295.CrossRefGoogle ScholarPubMed
Cohen, GM (1997) Caspases: the executioners of apoptosis. Biochemical Journal 326, 116.CrossRefGoogle ScholarPubMed
Cosentino, LShaver-Walker, P & Heddle, JA (1996) The relationships among stem|cells crypts, and villi in the small intestine of mice as determined by mutation tagging. Developmental Dynamics 207, 420428.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Cummings, JHPomare, EWBranch, WJNaylor, CPE & Macfarlane, GT (1987) Short chain fatty acids in human large intestine portal, hepatic and venous blood. Gut 28, 12211227.CrossRefGoogle ScholarPubMed
Das, UN (1991) Tumoricidal action of cis-unsaturated fatty acids and their relationship to free radicals and lipid peroxidation. Cancer Letters 56, 235243.CrossRefGoogle ScholarPubMed
De Filippo, CCaderni, GBazzicalupo, MBriani, CGiannini, AFazi, M & Dolara, P (1998) Mutations of the Apc gene in experimental colorectal carcinogenesis induced by azoxymethane in F344 rats. British Journal of Cancer 77, 21482151.CrossRefGoogle ScholarPubMed
Della Ragione, FCriniti, VDella Pietra, VBorriello, AOliva, AIndaco, SYamamoto, T & Zappia, V (2001) Genes modulated by histone acetylation as new affectors of butyrate activity. FEBS Letters 499, 199204.CrossRefGoogle Scholar
Deschner, EERuperto, JWong, G & Newmark, HL (1991) Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis 12, 11931196.CrossRefGoogle ScholarPubMed
Deveraux, QLStennicke, HRSalvesen, GS & Reed, JC (1999) Endogenous inhibitors of caspases. Journal of Clinical Immunology 19, 388398.CrossRefGoogle ScholarPubMed
de Wind, NDekker, MBerns, ARadman, M & te Riele, H (1995) Inactivation of the mouse Msh2 gene results in mismatch repair|deficiency methylation|tolerance hyperrecombination, and predisposition to cancer. Cell 82, 321330.CrossRefGoogle ScholarPubMed
Earnshaw, WCMartins, LM & Kaufmann, SH (1999) Mammalian caspases: structure, activation, substrates and functions during apoptosis. Annual Reviews of Biochemistry 68, 383424.CrossRefGoogle ScholarPubMed
Eberhart, CECoffey, RJRadhika, AGiardiello, FMFerrenbach, S & DuBois, RN (1994) Up-regulation of cyclo- oxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107, 11831188.CrossRefGoogle ScholarPubMed
Elder, DJHalton, DECrew, TE & Paraskeva, C (2000) Apoptosis induction and cyclooxygenase-2 regulation in human colorectal adenoma and carcinoma cell lines by the cyclooxygenase-2-selective non-steroidal anti-inflammatory drug NS-398. International Journal of Cancer 86, 553560.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Ellis, HM & Horvitz, HR (1986) Genetic control of programmed cell death in the nematode C. elegans Cell 44, 817829.CrossRefGoogle ScholarPubMed
Fadeel, BOrrenius, S & Zhivotovsky, B (2000) The most unkindest cut of all: on the multiple roles of mammalian caspases. Leukemia 14, 15141525.CrossRefGoogle ScholarPubMed
Farber, E (1995) Cell proliferation as a major risk factor for cancer: a concept of doubtful validity. Cancer Research 55, 37593762.Google Scholar
Fay, MPFreedman, LSClifford, CK & Midthune, DN (1997) Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Research 57, 39793988.Google ScholarPubMed
Fearon, ERHamilton, SR & Vogelstein, B (1987) Clonal analysis of human colorectal tumors. Science 238, 193197.CrossRefGoogle ScholarPubMed
Fenwick, GRHeaney, RK & Mullin, WJ (1983) Glucosinolates and their breakdown products in food and food plants. Critical Reviews in Food Science and Nutrition 18, 123201.CrossRefGoogle ScholarPubMed
Finstad, HSMyhrstad, MCHeimli, HLomo, JBlomhoff, HKKolset, SO & Drevon, CA (1998) Multiplication and death-type of leukemia cell lines exposed to very long-chain polyunsaturated fatty acids. Leukemia 12, 921929.CrossRefGoogle ScholarPubMed
Flemming, W (1885) Uber die Bildung von Richtungsfiguren in Saugerthiereiern beim Untergang Graaf scher Follikel (On interpreting the regression of ammalian lymphoid follicles). Archiv für Anatomie und Entwicklungsgeschichte 1885, 221224.Google Scholar
Formica, JV & Regelson, W (1995) Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology 33, 10611080.CrossRefGoogle ScholarPubMed
Frisch, SM & Francis, H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. Journal of Cell Biology 124, 619626.CrossRefGoogle ScholarPubMed
Fussenegger, MBailey, JE & Varner, J (2000) A mathematical model of caspase function in apoptosis. Nature Biotechnology 18, 768774.CrossRefGoogle ScholarPubMed
Gafa, R & Lanza, G (1998) Expression of protein p53 in the adenoma-colorectal carcinoma sequence. Pathologica 90, 351356.Google ScholarPubMed
Gali, HUPerchellet, EM & Perchellet, JP (1991) Inhibition of tumor promoter-induced ornithine decarboxylase activity by tannic acid and other polyphenols in mouse epidermis in vivo. Cancer Research 51, 28202825.Google ScholarPubMed
Gann, PHManson, JEGlynn, RJBuring, JE & Hennekens, CH (1993) Low-dose aspirin and incidence of colorectal tumors in a randomized trial. Journal of the National Cancer Institute 85, 12201224.CrossRefGoogle ScholarPubMed
Glucksmann, A (1951) Cell deaths in normal vertebrate ontogeny. Biological Reviews of the Cambridge Philosophical Society 26, 5986.CrossRefGoogle ScholarPubMed
Goodlad, RALenton, WGhatei, MAAdrian, TEBloom, SR & Wright, NA (1987) Proliferative effects of ‘fibre’ on the intestinal epithelium: relationship to gastrin enteroglucagon and PYY. Gut 28, 221226.CrossRefGoogle ScholarPubMed
Goodlad, RALevi, SLee, CYMandir, NHodgson, H & Wright, NA (1991) Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique. Gastroenterology 101, 12351241.CrossRefGoogle ScholarPubMed
Graper, L (1914) Eine neue Anschauung uber physiologische Zellausschaltung (A new outlook on physiological cell deletion). Archiv für Zellforschung 13, 373374.Google Scholar
Groden, JNakamura, Y & German, J (1990) Molecular evidence that homologous recombination occurs in proliferating human somatic cells. Proceedings of the National Academy of Sciences USA 87, 43154319.CrossRefGoogle ScholarPubMed
Grossmann, JArtinger, MGrasso, AWKung, HJScholmerich, JFiocchi, C & Levine, AD (2001) Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells. Gastroenterology 120, 7988.CrossRefGoogle ScholarPubMed
Hagopian, HKRiggs, MGSwartz, LA & Ingram, VM (1977) Effect of n-butyrate on DNA synthesis in chick fibroblasts and HeLa cells. Cell 12, 855860.CrossRefGoogle ScholarPubMed
Hague, AElder, DJHicks, 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. International Journal of Cancer 60, 400406.CrossRefGoogle ScholarPubMed
Hague, AManning, AMHanlon, KAHuschtscha, LIHart, D & Paraskeva, C (1993) Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of large-bowel cancer. International Journal of Cancer 55, 498505.CrossRefGoogle Scholar
Halliwell, BZhao, K & Whiteman, M (2000) The gastrointestinal tract: a major site of antioxidant action? Free Radical Research 33, 819830.CrossRefGoogle Scholar
Hara, HGee, JM & Johnson, IT (1999) Antiproliferative effects of quercetin in the rat gastrointestinal tract. In Proceedings of the Seventh Scientific Workshop of COST 98, vol. EUR 19229 EN, pp. 4953 [Krogdahl, AMathieson, SD and Pryme, IF editors ]. Brussels: European Commission.Google Scholar
Hardman, WECameron, ILHeitman, DW & Contreras, E (1991) Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence. Cancer Research 51, 63886392.Google ScholarPubMed
Harig, JMSoergel, KHKomorowski, RA & Wood, CM (1989) Treatment of diversion colitis with short chain fatty acid irrigation. New England Journal of Medicine 320, 2328.CrossRefGoogle ScholarPubMed
Hasegawa, TNishino, H & Iwashima, A (1993) Isothiocyanates inhibit cell cycle progression of HeLa cells at G2/M phase. Anticancer Drugs 4, 273279.CrossRefGoogle ScholarPubMed
Hass, RBusche, RLuciano, LReale, E & Engelhardt, WV (1997) Lack of butyrate is associated with induction of Bax and subsequent apoptosis in the proximal colon of guinea pig. Gastroenterology 112, 875881.CrossRefGoogle ScholarPubMed
Hawkins, RASangster, K & Arends, MJ (1998) Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism. Journal of Pathology 185, 6170.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Hecht, SS (1999) Chemoprevention of cancer by isothiocyanates modifiers of carcinogen metabolism. Journal of Nutrition 129, 768S774S.CrossRefGoogle ScholarPubMed
Hecht, SSChung, FLRichie, JP Jr, Akerkar, SABorukhova, ASkowronski, L & Carmella, SG (1995) Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiology Biomarkers and Prevention 4, 877884.Google ScholarPubMed
Hecht, SSTrushin, NRigotty, JCarmella, SGBorukhova, AAkerkar, SDesai, DAmin, S & Rivenson, A (1996) Inhibitory effects of 6-phenylhexyl isothiocyanate on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolic activation and lung tumorigenesis in rats. Carcinogenesis 17, 20612067.CrossRefGoogle ScholarPubMed
Heddle, JACosentino, LDawod, GSwiger, RR & Paashuis-Lew, Y (1996) Why do stem cells exist? Environmental and Molecular Mutagenesis 28, 334341.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Heerdt, BGHouston, MA & Augenlicht, LH (1994) Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines. Cancer Research 54, 32883293.Google ScholarPubMed
Hertog, MGHollman, PCKatan, MB & Kromhout, D (1993) Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutrition and Cancer 20, 2129.CrossRefGoogle ScholarPubMed
Hill, MJMorson, BC & Bussey, HJ (1978) Aetiology of adenoma—carcinoma sequence in large bowel. Lancet i, 245247.CrossRefGoogle Scholar
Hoff, GMoen, IETrygg, KFrolich, WFoerster, AVatn, MSauar, J & Larsen, S (1988) Colorectal adenomas and food. A prospective study of change in volume and total mass of adenomas in man. Scandinavian Journal of Gastroenterology 23, 12531258.CrossRefGoogle ScholarPubMed
Hursting, SDThornquist, M & Henderson, MM (1990) Types of dietary fat and the incidence of cancer at five sites. Preventative Medicine 19, 242253.CrossRefGoogle ScholarPubMed
Jacobs, LR & Lupton, JR (1986) Relationship between colonic luminal pH cell proliferation and colon carcinogenesis in 1,2-dimethylhydrazine treated rats fed high fiber diets. Cancer Research 46, 17271734.Google ScholarPubMed
James, JT & Autrup, H (1983) Methylated DNA adducts in the large intestine of ICR/Ha and C57BL/Ha mice given 1,2-dimethylhydrazine. Journal of the National Cancer Institute 70, 541546.Google ScholarPubMed
Kargman, SLO'Neill, GPVickers, PJEvans, JFMancini, JA & Jothy, S (1995) Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Research 55, 25562559.Google Scholar
Kashtan, HStern, HSJenkins, DJJenkins, ALThompson, LUHay, KMarcon, NMinkin, S & Bruce, WR (1992) Colonic fermentation and markers of colorectal-cancer risk. American Journal of Clinical Nutrition 55, 723728.CrossRefGoogle ScholarPubMed
Kerr, JF (1971) Shrinkage necrosis: a distinct mode of cellular death. Journal of Pathology 105, 1320.CrossRefGoogle ScholarPubMed
Kerr, JFWyllie, AH & Currie, AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26, 239257.CrossRefGoogle ScholarPubMed
Kinzler, KW & Vogelstein, B (1996) Lessons from hereditary colorectal cancer. Cell 87, 159170.CrossRefGoogle ScholarPubMed
Kluck, RMBossy-Wetzel, EGreen, DR & Newmeyer, DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 11321136.CrossRefGoogle ScholarPubMed
Kozoni, VTsioulias, GShiff, S & Rigas, B (2000) The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: differential effect on apoptosis in the presence of a colon carcinogen. Carcinogenesis 21, 9991005.CrossRefGoogle ScholarPubMed
Kripke, SAFox, AD & Berman, JR (1989) Stimulation of intestinal mucosal growth with intracolonic infusion of short chain fatty acids. Journal of Parenteral and Enteral Nutrition 13, 109116.CrossRefGoogle ScholarPubMed
Kuida, KLippke, JAKu, GHarding, MWLivingston, DJSu, MS & Flavell, RA (1995) Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 267, 20002003.CrossRefGoogle ScholarPubMed
Kuntz, SWenzel, U & Daniel, H (1999) Comparative analysis of the effects of flavonoids on proliferation cytotoxicity, and apoptosis in human colon cancer cell lines. European Journal of Nutrition 38, 133142.CrossRefGoogle ScholarPubMed
Kuwana, TSmith, JJMuzio, MDixit, VNewmeyer, DD & Kornbluth, S (1998) Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. Journal of Biological Chemistry 273, 1658916594.CrossRefGoogle ScholarPubMed
Lamlum, HPapadopoulou, AIlyas, MRowan, AGillet, CHanby, ATalbot, IBodmer, W & Tomlinson, I (2000) APC mutations are sufficient for the growth of early colorectal adenomas. Proceedings of the National Academy of Sciences USA 97, 22252228.CrossRefGoogle ScholarPubMed
Lancaster, T & Silagy, C (1994) Aspirin and neoplasia of the digestive tract: is there a chemopreventive effect? Digestive Diseases 12, 170176.CrossRefGoogle Scholar
Latham, PLund, EKBrown, JC & Johnson, IT (2001) Effects of cellular redox balance on induction of apoptosis by eicosapentaenoic acid in HT29 colorectal adenocarcinoma cells and rat colon in vivo. Gut 49, 97105.CrossRefGoogle ScholarPubMed
Latham, PLund, EK & Johnson, IT (1998) Modulation of colonocyte proliferation and apoptosis by dietary fish oil in experimental colorectal carcinogenesis. Biochemical Society Transactions 26, S158.CrossRefGoogle ScholarPubMed
Latham, PLund, EK & Johnson, IT (1999) Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon. Carcinogenesis 20, 645650.CrossRefGoogle ScholarPubMed
Lea, MARandolph, VMLee, JE & desBourdes, C (2001) Induction of histone acetylation in mouse erythroleukemia cells by organosulfur compounds including acetyl isothiocyanate. International Journal of Cancer 92, 784789.CrossRefGoogle Scholar
Lee, FD (1993) Importance of apoptosis in the histopathology of drug related lesions in the large intestine. Journal of Clinical Pathology 46, 118122.CrossRefGoogle ScholarPubMed
Lennard-Jones, J (2001) Annual Review. London: Digestive Disorders Foundation.Google Scholar
Li, MOna, VOChen, MKaul, MTenneti, LZhang, XStieg, PELipton, SA & Friedlander, RM (2000) Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 99, 333342.CrossRefGoogle Scholar
Lin, HJProbst-Hensch, NMLouie, ADKau, IHWitte, JSIngles, SAFrankl, HDLee, ER & Haile, RW (1998) Glutathione transferase null genotype broccoli, and lower prevalence of colorectal adenomas. Cancer Epidemiology Biomarkers and Prevention 7, 647652.Google ScholarPubMed
Loeb, LA (1994) Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Research 54, 50595063.Google ScholarPubMed
Loeb, LA (1998) Cancer cells exhibit a mutator phenotype. Advances in Cancer Research 72, 2556.CrossRefGoogle ScholarPubMed
Loeffler, MBirke, AWinton, D & Potten, C (1993) Somatic mutation monoclonality and stochastic models of stem cell organization in the intestinal crypt. Journal of Theoretical Biology 160, 471491.CrossRefGoogle ScholarPubMed
Lund, EK & Johnson, IT (1991) Fermentable carbohydrate reaching the colon after ingestion of oats in humans. Journal of Nutrition 121, 311317.CrossRefGoogle ScholarPubMed
Lund, EKSmith, TKLatham, P Clarke R & Johnson IT (2000) Influence of biologically active food constituents on apoptosis and cell cycle in colorectal epithelial cells. In Dietary Anticarcinogens and Antimutagens: Chemical and Biological Aspects, pp. 333337 [Johnson, IT and Genwick, GR editors ]. Cambridge: Royal Society of Chemistry.CrossRefGoogle Scholar
Lutz, WK & Schlatter, J (1992) Chemical carcinogens and overnutrition in diet-related cancer. Carcinogenesis 13, 22112216.CrossRefGoogle ScholarPubMed
Lynch, HT & Krush, AJ (1971) Cancer family ‘G’ revisited: 1895–1970. Cancer 27, 15051511.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Majno, G & Joris, I (1999) Commentary: On the misuse of the term ‘necrosis’: a step in the right direction. Toxicologic Pathology 27, 494.CrossRefGoogle ScholarPubMed
Mandal, MOlson, DJSharma, TVadlamudi, RK & Kumar, R (2001) Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells. Gastroenterology 120, 7178.CrossRefGoogle ScholarPubMed
Markowitz, AJ & Winawer, SJ (1999) Screening and surveillance for colorectal cancer. Seminars in Oncology 26, 485498.Google ScholarPubMed
Marx, J (2001) Cancer research. Science 291, 581582.CrossRefGoogle ScholarPubMed
Maskens, AP & Dujardin-Loits, RM (1981) Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa. Cancer 47, 8189.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Matsukawa, YNishino, HOkuyama, YMatsui, TMatsumoto, TMatsumura, SShimizu, YSowa, Y & Sakai, T (1997) Effects of quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons. Oncology 54, 118121.CrossRefGoogle ScholarPubMed
Matthew, JAPell, JDPrior, AKennedy, HJFellows, IWGee, JMBurton, J & Johnson, IT (1994) Validation of a simple technique for the detection of abnormal mucosal cell replication in humans. European Journal of Cancer Prevention 3, 337344.CrossRefGoogle ScholarPubMed
Merritt, AJPotten, CSKemp, CJHickman, JABalmain, ALane, DP & Hall, PA (1994) The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Research 54, 614617.Google ScholarPubMed
Merritt, AJPotten, CSWatson, AJLoh, DYNakayama, K & Hickman, JA (1995) Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. Journal of Cell Science 108, 22612271.CrossRefGoogle ScholarPubMed
Mithen, RFDekker, MVerkerk, RRabot, S & Johnson, IT (2000) The nutritional significance biosynthesis and bioavailability of glucosinolates in human foods. Journal of the Science of Food and Agriculture 80, 967984.3.0.CO;2-V>CrossRefGoogle Scholar
Miura, MZhu, HRotello, RHartwieg, EA & Yuan, J (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75, 653660.CrossRefGoogle ScholarPubMed
Mortensen, FVHessov, IBirke, HKorsgaard, N & Nielsen, H (1991) Microcirculatory and trophic effects of short chain fatty acids in the human rectum after Hartmann's procedure. British Journal of Surgery 78, 12081211.CrossRefGoogle ScholarPubMed
Mortensen, PB & Clausen, MR (1996) Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scandinavian Journal of Gastroenterology 31, Suppl. 216, 132148.CrossRefGoogle Scholar
Musk, SR & Johnson, IT (1993) Allyl isothiocyanate is selectively toxic to transformed cells of the human colorectal tumour line HT29. Carcinogenesis 14, 20792083.CrossRefGoogle ScholarPubMed
Musk, SRStephenson, PSmith, TKStening, PFyfe, D & Johnson, IT (1995) Selective toxicity of compounds naturally present in food toward the transformed phenotype of human colorectal cell line HT29. Nutrition and Cancer 24, 289298.CrossRefGoogle ScholarPubMed
Muzio, M (1998) Signalling by proteolysis: death receptors induce apoptosis. International Journal of Clinical and Laboratory Research 28, 141147.CrossRefGoogle ScholarPubMed
Nijhoff, WAGrubben, MJNagengast, FMJansen, JBVerhagen, Hvan Poppel, G & Peters, WH (1995) Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans. Carcinogenesis 16, 21252128.CrossRefGoogle ScholarPubMed
Palmerini, FDevilard, EJarry, ABirg, F & Xerri, L (2001) Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma. Human Pathology 32, 461467.CrossRefGoogle ScholarPubMed
Palozza, PCalviello, GSerini, SMaggiano, NLanza, PRaneletti, FO & Bartoli, GM (2001) β-Carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells. Free Radicals in Biology and Medicine 30, 10001007.CrossRefGoogle ScholarPubMed
Partik, GKahl-ainer, PSedivy, REllinger, ABursch, W & Marian, B (1998) Apoptosis in human colorectal tumours: ultrastructure and quantitative studies on tissue localization and association with bak expression. Virchows Archiv 432, 415426.CrossRefGoogle ScholarPubMed
Pasricha, PJBedi, AO' Connor, KRashid, AAkhtar, AJZahurak, MLPiantadosi, SHamilton, SR & Giardiello, FM (1995) The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis. Gastroenterology 110, 13231324.Google Scholar
Pell, JDBrown, JC & Johnson, IT (1994) Polyunsaturated fatty acids of the n-3 series influence intestinal crypt cell production in rats. Carcinogenesis 15, 11151119.CrossRefGoogle ScholarPubMed
Pell, JDJohnson, IT & Goodlad, RA (1995) The effects of and interactions between fermentable dietary fiber and lipid in germfree and conventional mice. Gastroenterology 108, 17451752.CrossRefGoogle ScholarPubMed
Perrin, PPierre, FPatry, YChamp, MBerreur, MPradal, GBornet, FMeflah, K & Menanteau, J (2001) Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut 48, 5361.CrossRefGoogle ScholarPubMed
Piazza, GARahm, ALKrutzsch, MSperl, GParanka, NSGross, PHBrendel, KBurt, RWAlberts, DSPamukcu, R & Ahnen, DJ (1995) Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Research 55, 31103116.Google ScholarPubMed
Pollard, M & Luckert, PH (1980) Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. Cancer Treatment Reports 64, 13231327.Google ScholarPubMed
Polyak, KXia, YZweier, JLKinzler, KW & Vogelstein, B (1997) A model for p53-induced apoptosis. Nature 389, 300305.CrossRefGoogle Scholar
Potten, CS (1986) Cell cycles in cell hierarchies. International Journal of Radiation Biology and Related Studies in Physics Chemistry, and Medicine 49, 257278.CrossRefGoogle ScholarPubMed
Potten, CS (1992) The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice. Cancer Metastasis Reviews 11, 179195.CrossRefGoogle ScholarPubMed
Potten, CSLi, YQO'Connor, PJ & Winton, DJ (1992) A possible explanation for the differential cancer incidence in the intestine based on distribution of the cytotoxic effects of carcinogens in the murine large bowel. Carcinogenesis 13, 23052312.CrossRefGoogle ScholarPubMed
Potten, CS & Morris, RJ (1988) Epithelial stem cells in vivo. Journal of Cell Science 10, 4562.CrossRefGoogle ScholarPubMed
Preston-Martin, SPike, MCRoss, RKJones, PA & Henderson, BE (1990) Increased cell division as a cause of human cancer. Cancer Research 50, 74157421.Google ScholarPubMed
Pretlow, TPBarrow, BJAshton, WSO'Riordan, MAPretlow, TGJurcisek, JA & Stellato, TA (1991) Aberrant crypts: putative preneoplastic foci in human colonic mucosa. Cancer Research 51, 15641567.Google ScholarPubMed
Pritchard, DMPotten, CS & Hickman, JA (1998) The relationship between p53- dependent|apoptosis inhibition of proliferation and 5-fluorouracil-induced histopathology in murine intestinal epithelia. Cancer Research 58, 54535465.Google ScholarPubMed
Pritchard, DMPrint, C O' Reilly, LAdams, JMPotten, CS & Hickman, JA (2000) Bcl-w is an important determinant of damage-induced apoptosis in epithelia of small and large intestine. Oncogene 19, 39553959.CrossRefGoogle ScholarPubMed
Ramesh, G & Das, UN (1998) Effect of cis-unsaturated fatty acids on Meth-A ascitic tumour cells in vitro and in vivo. Cancer Letters 123, 207214.CrossRefGoogle ScholarPubMed
Reddy, BS (1992) Dietary fat and colon cancer: animal model studies. Lipids 27, 807813.CrossRefGoogle ScholarPubMed
Reinacher-Schick, ASeidensticker, FPetrasch, SReiser, MPhilippou, STheegarten, DFreitag, G & Schmiegel, W (2000) Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel. Endoscopy 32, 245254.CrossRefGoogle ScholarPubMed
Roberts, SAHendry, JH & Potten, CS (1995) Deduction of the clonogen content of intestinal crypts: a direct comparison of two-dose and multiple-dose methodologies. Radiation Research 141, 303308.CrossRefGoogle ScholarPubMed
Roberts, SA & Potten, CS (1994) Clonogen content of intestinal crypts: its deduction using a microcolony assay on whole mount preparations and its dependence on radiation dose. International Journal of Radiation Biology 65, 477481.CrossRefGoogle ScholarPubMed
Roediger, WE (1990) The starved colon – diminished mucosal nutrition diminished|absorption and colitis. Diseases of Colon and Rectum 33, 858862.CrossRefGoogle ScholarPubMed
Roncucci, LPedroni, MVaccina, FBenatti, PMarzona, L & De Pol, A (2000) Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics. Cell Proliferation 33, 118.CrossRefGoogle ScholarPubMed
Rubio, CAHubbard, GB & Frost, P (2001) Apoptotic colonic disease: a new entity in a primate. In Vivo 15, 3537.Google ScholarPubMed
Ruemmele, FRuemmele, CLevy, E & Seidman, E (1999) Les mecanismes moleculaires de la regulation du renouvellement des cellules epitheliales intestinales par des nutriments (Molecular mechanisms for the regulation of intestinal epithelial cell renewal by nutrients). Gastroenterologie Clinique et Biologique 23, 4755.Google Scholar
Sakata, T & von Engelhardt, W (1983) Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in rat large intestine. Comparative Biochemistry and Physiology 74, 459462.CrossRefGoogle ScholarPubMed
Sano, HKawahito, YWilder, RLHashiramoto, AMukai, SAsai, KKimura, SKato, HKondo, M & Hla, T (1995) Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Research 55, 37853789.Google ScholarPubMed
Schloss, IKidd, MSTichelaar, HYYoung, GO & O'Keefe, SJ (1997) Dietary factors associated with a low risk of colon cancer in coloured west coast fishermen. South African Medical Journal 87, 152158.Google ScholarPubMed
Shiff, SJQiao, LTsai, LL & Rigas, B (1995) Sulindac sulfide an aspirin-like compound inhibits proliferation causes cell cycle quiescence and induces apoptosis in HT-29 colon adenocarcinoma cells. Journal of Clinical Investigation 96, 491503.CrossRefGoogle ScholarPubMed
Shih, IMWang, TLTraverso, GRomans, KHamilton, SRBen-Sasson, SKinzler, KW & Vogelstein, B (2001) Top-down morphogenesis of colorectal tumors. Proceedings of the National Academy of Sciences USA 98, 26402645.CrossRefGoogle ScholarPubMed
Shivapurkar, NTang, ZFerreira, ANasim, SGarett, C & Alabaster, O (1994) Sequential analysis of K-ras mutations in aberrant crypt foci and colonic tumors induced by azoxymethane in Fischer-344 rats on high-risk diet. Carcinogenesis 15, 775778.CrossRefGoogle ScholarPubMed
Siavoshian, SSegain, JPKornprobst, MBonnet, CCherbut, CGalmiche, JP & Blottiere, HM (2000) Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression. Gut 46, 507514.CrossRefGoogle ScholarPubMed
Singh, BHalestrap, AP & Paraskeva, C (1997) Butyrate can act as a stimulator of growth or inducer of apoptosis in human colonic epithelial cell lines depending on the presence of alternative energy sources. Carcinogenesis 18, 12651270.CrossRefGoogle ScholarPubMed
Smith, AJStern, HSPenner, MHay, KMitri, ABapat, BV & Gallinger, S (1994) Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons. Cancer Research 54, 55275530.Google ScholarPubMed
Smith, MLHawcroft, G & Hull, MA (2000) The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action. European Journal of Cancer 36, 664674.CrossRefGoogle ScholarPubMed
Smith, TKClarke, RScott, J & Johnson, IT (2000 b) Raw Brussels sprouts block mitosis in colorectal cancer cells (HT29) and induce apoptosis in rat colonic mucosal crypts in vivo. In Dietary Anticarcinogens and Antimutagens: Chemical and Biological Aspects [Johnson, IT and Fenwick, GR editors ]. Cambridge: Royal Society of Chemistry.Google Scholar
Smith, TKLund, EK & Johnson, IT (1998) Inhibition of dimethylhydrazine-induced aberrent crypt foci and induction of apoptosis in rat colon following oral administration of the glucosinolate sinigrin. Carcinogenesis 19, 267273.CrossRefGoogle Scholar
Soussi, T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Annals of the New York Academy of Sciences 910, 121137.CrossRefGoogle ScholarPubMed
Steinbach, GLynch, PMPhillips, RKWallace, MHHawk, EGordon, GBWakabayashi, NSaunders, BShen, YFujimura, TSu, LK & Levin, B (2000) The effect of celecoxib a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New England Journal of Medicine 342, 19461952.CrossRefGoogle ScholarPubMed
Stoner, GDBudd, GTGanapathi, RDeYoung, BKresty, LANitert, MFryer, BChurch, JMProvencher, KPamukcu, RPiazza, GHawk, EKelloff, GElson, P & van Stolk, RU (1999) Sulindac sulfone induced regression of rectal polyps in patients with familial adenomatous polyposis. Advances in Experimental Medicine and Biology 470, 4553.CrossRefGoogle ScholarPubMed
Strater, JWellisch, IRiedl, SWalczak, HKoretz, KTandara, AKrammer, PH & Moller, P (1997) CD95(APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 113, 345348.CrossRefGoogle ScholarPubMed
Sulston, JE & Horvitz, HR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental Biology 56, 110156.Google ScholarPubMed
Takayama, TKatsuki, STakahashi, YOhi, MNojiri, SSakamaki, SKato, JKogawa, KMiyake, H & Niitsu, Y (1998) Aberrant crypt foci of the colon as precursors of adenoma and cancer. New England Journal of Medicine 339, 12771284.CrossRefGoogle ScholarPubMed
Tannenbaum, A & Silverstone, H (1953) Nutrition in relation to cancer. Advances in Cancer Research 1, 451465.CrossRefGoogle ScholarPubMed
Toft, NJWinton, DJKelly, JHoward, LADekker, Mte Riele, HArends, MJWyllie, AHMargison, GP & Clarke, AR (1999) Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine. Proceedings of the National Academy of Sciences USA 96, 39113915.CrossRefGoogle ScholarPubMed
Tomlinson, I & Bodmer, W (1999) Selection, the mutation rate and cancer: ensuring that the tail does not wag the dog. Nature Medicine 5, 1112.CrossRefGoogle Scholar
Tomlinson, IP & Bodmer, WF (1995) Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models. Proceedings of the National Academy of Sciences USA 92, 1113011134.CrossRefGoogle ScholarPubMed
Tomlinson, IPNovelli, MR & Bodmer, WF (1996) The mutation rate and cancer. Proceedings of the National Academy of Sciences USA 93, 1480014803.CrossRefGoogle ScholarPubMed
Tong, CFazio, M & Williams, GM (1980) Cell-cycle specific mutagenesis at the hypoxanthine phosphoribosyltransferase locus in adult rat liver epithelial cells. Proceedings of the National Academy of Sciences USA 77, 73777379.CrossRefGoogle ScholarPubMed
Tsujii, M & DuBois, RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83, 493501.CrossRefGoogle ScholarPubMed
Vane, JR & Botting, RM (1998) Mechanism of action of antiinflammatory drugs. International Journal of Tissue Reactions 20, 315.Google ScholarPubMed
van Poppela, GVerhoeven, DTVerhagen, H & Goldbohm, RA (1999) Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Advances in Experimental Medicine and Biology 472, 159168.CrossRefGoogle Scholar
Virchow, R and Chandler, AB (1859) Cellular Pathology as Based upon Physiological and Pathological Histology. New York: Dover Publications.Google Scholar
Vogelstein, BFearon, ERHamilton, SRKern, SEPreisinger, ACLeppert, MNakamura, YWhite, RSmits, AM & Bos, JL (1988) Genetic alterations during colorectal-tumor development. New England Journal of Medicine 319, 525532.CrossRefGoogle ScholarPubMed
Vogelstein, BLane, D & Levine, AJ (2000) Surfing the p53 network. Nature 408, 307310.CrossRefGoogle ScholarPubMed
Voorrips, LEGoldbohm, RAvan Poppel, GSturmans, FHermus, RJ & van den Brandt, PA (2000) Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer. American Journal of Epidemiology 152, 10811092.CrossRefGoogle Scholar
Waddell, WR (1998) Stimulation of apoptosis by sulindac and piroxicam. Clinical Science (Colchester) 95, 385388.CrossRefGoogle ScholarPubMed
Waddell, WRGanser, GFCerise, EJ & Loughry, RW (1989) Sulindac for polyposis of the colon. American Journal of Surgery 157, 175179.CrossRefGoogle ScholarPubMed
Wallach, D (1997) Apoptosis. Placing death under control. Nature 388, 123, 125126.CrossRefGoogle ScholarPubMed
Wasan, HS & Goodlad, RA (1996) Fibre-supplemented foods may damage your health. Lancet 348, 319320.CrossRefGoogle ScholarPubMed
Wenzel, UKuntz, SBrendel, MD & Daniel, H (2000) Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells. Cancer Research 60, 38233831.Google ScholarPubMed
Wheeler, JMBodmer, WF & Mortensen, NJ (2000) DNA mismatch repair genes and colorectal cancer. Gut 47, 148153.CrossRefGoogle ScholarPubMed
Winawer, SJ (1999) Natural history of colorectal cancer. American Journal of Medicine 106, 3S6S.CrossRefGoogle ScholarPubMed
Wright, N & Alison, M (1984) Cell proliferation in gastrointestinal carcinogenesis. The Biology of Epithelial Cell Populations, vol. 2, pp. 823825. Oxford: Clarendon Press.Google Scholar
Wu, JTArcher, SYHinnebusch, BMeng, S and Hodin RA (2001) Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth differentiation, and apoptosis. American Journal of Physiology Gastrointestinal and Liver Physiology 280, G482G490.CrossRefGoogle ScholarPubMed
Wyllie, AHBellamy, COBubb, VJClarke, ARCorbet, SCurtis, LHarrison, DJHooper, MLToft, NWebb, S & Bird, CC (1999) Apoptosis and carcinogenesis. British Journal of Cancer 80, Suppl. 1, 3437.Google ScholarPubMed
Wyllie, AHKerr, JF & Currie, AR (1980) Cell death: the significance of apoptosis. International Reviews in Cytology 68, 251306.CrossRefGoogle ScholarPubMed
Xu, K & Thornalley, PJ (2000) Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro. Biochemical Pharmacology 60, 221231.CrossRefGoogle ScholarPubMed
Yamamoto, MTsukamoto, TSakai, HShirai, NOhgaki, HFurihata, CDonehower, LAYoshida, K & Tatematsu, M (2000) p53 knockout mice (-/-) are more susceptible than (+/-) or (+/+) mice to N-methyl-N-nitrosourea stomach carcinogenesis. Carcinogenesis 21, 18911897.CrossRefGoogle Scholar
Yang, KLamprecht, SALiu, YShinozaki, HFan, KLeung, DNewmark, HSteele, VEKelloff, GJ & Lipkin, M (2000) Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis 21, 16551660.CrossRefGoogle ScholarPubMed
Yeh, WCItie, AElia, AJNg, MShu, HBWakeham, AMirtsos, CSuzuki, NBonnard, MGoeddel, DV & Mak, TW (2000) Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 12, 633642.CrossRefGoogle ScholarPubMed
Yin, XM (2000) Signal transduction mediated by Bid a pro-death Bcl-2 family protein connects death receptor and mitochondria apoptosis pathways. Cell Research 10, 161167.CrossRefGoogle Scholar
Yoshida, MYamamoto, M & Nikaido, T (1992) Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. Cancer Research 52, 66766681.Google ScholarPubMed
Yu, RJiao, JJDuh, JLTan, TH & Kong, AN (1996) Phenethyl isothiocyanate a natural chemopreventive agent activates c-Jun N-terminal kinase 1. Cancer Research 56, 29542959.Google ScholarPubMed
Yu, RMandlekar, SHarvey, KJUcker, DS & Kong, AN (1998) Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity. Cancer Research 58, 402408.Google ScholarPubMed
Yuan, JShaham, SLedoux, SEllis, HM & Horvitz, HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641652.CrossRefGoogle Scholar
Zhang, HRichards, BWilson, TLloyd, MCranston, AThorburn, AFishel, R & Meuth, M (1999) Apoptosis induced by overexpression of hMSH2 or hMLH1. Cancer Research 59, 30213027.Google ScholarPubMed
Zsolnai, T (1971) Antimicrobial effects of thiocyanates isothiocyanates and potential isothiocyanate forming substances. Arzneimittelforschung 21, 121127.Google ScholarPubMed