Abstract
Ten years have passed since rodent models of experimental pancreatic carcinogenesis were last reviewed in the first edition of Digestive System in this monograph series. At the time of that review (Scarpelli et al. 1985), it was clear that the exocrine pancreas of rodent species was susceptible to a variety of chemical carcinogens and that these might be models of utility for pathogenetic and other analyses of the carcinogenic process. A remarkable feature of these models is that in various rodent species different types of exocrine cells appear to be susceptible to the neoplastic transformation. For example, in the rat and guinea pig, the majority of tumors induced are acinar cell adenomas and carcinomas, as contrasted to the hamster, in which almost exclusively ductal adenocarcinomas develop. In mice, on the other hand, both acinar cell carcinomas and duct-like carcinomas have been obtained.
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References
Andrén-Sandberg A (1989) Androgen influence on exocrine pancreatic cancer. Int J Pancreatol 4:363–369
Arias AE, Bendayan M (1993) Differentiation of pancreatic acinar cells into duct-like cells in vitro. Lab Invest 69:518–530
Bakkevold KE, Pettersen A, Amesjo B, Espehaug B (1990) Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and the papilla of vater. Br J Surg 77:725–730
Barton C, Hall PA, Hughes CM, Gullick WJ, Lemoine NR (1991) Transforming growth factor α and epidermal growth factor in human pancreatic cancer. J Pathol 163:111–116
Bell RH Jr, Kuhlmann ET, Jensen RT, Longnecker DS (1992) Overexpression of cholecystokinin receptors in azaserine-induced neoplasms of the rat pancreas. Cancer Res 52:3295–3299
Berenblum I, Shubik P (1947) A new quantitative approach to the study of the stages of chemical carcinogenesis in the mouse’s skin. Br J Cancer 1:383–391
Birt DF, Pour PM (1987) Pancreatic cancer enhancement in the hamster model by diets high in fat and/or protein. In: Scarpelli DG, Reddy JK, Longnecker DS (eds) Experimental pancreatic carcinogenesis. CRC Press, Boca Raton, FL, pp 175–186
Birt DF, Stepan KR, Pour PM (1983) Interaction of dietary fat and protein on pancreatic carcinogenesis in Syrian golden hamsters. J Natl Cancer Inst 71:355–360
Birt DF, Julius AD, White LT, Pour PM (1989) Enhancement of pancreatic carcinogenesis in hamsters fed a high-fat diet ad libitum and at a controlled calorie intake. Cancer Res 49:5848–5851
Birt DF, Julius AD, Dwork E, Hanna T, White LT, Pour PM (1990) Comparison of the effects of dietary beef tallow and corn oil on pancreatic carcinogenesis in the hamster model. Carcinogenesis 11:745–748
Bos JL (1989) ras oncogene in human cancer: a review. Cancer Res 49:4682–4689
Buscail L, Delesque N, Estève JP, Saint-Laurent N, Prats H, Clerc P, Rofferecht P, Bell Gl, Liebow C, Schally AV, Voysse N, Susini C (1994) Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 91:2315–2319
Cerny WL, Marigold KA, Scarpelli DG (1990) Activation of K-ras in transplantable pancreatic ductal adenocarcinomas of Syrian golden hamsters. Carcinogenesis 11:2075–2079
Cerny WL, Marigold KA, Scarpelli DG (1992) K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster. Cancer Res 52:4507–4513
Chang K-W, Laconi S, Mangold KA, Hubchak S, Scarpelli DG (1995) Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas. Cancer Res 55:2560–2568
DeLisle RC, Logsdon CD (1990) Pancreatic acinar cells in culture: expression of acinar and ductal antigens in a growth-related manner. Eur J Cell Biol 51:64–75
Douglas BR, Woutersen RA, Jansen JB, de Jong AJL, Rovati LC, Lamers CB (1989) Modulation by CR-1409 (Lorglumide), a cholecystokinin receptor antagonist, of trypsin inhibitor-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas. Cancer Res 49:2438–2441
Falk RT, Pickle LW, Fontham ET, Correa P, Fraumeni JF Jr (1988) Life-style risk factors for pancreatic cancer in Louisiana: a case control study. Am J Epidemiol 128:324–336
Farber E (1984) The multistep nature of cancer development. Cancer Res 44:4217–4223
Farrow DC, Davis S (1990) Diet and the risk of pancreatic cancer in men. Am J Epidemiol 132:423–431
Fekete M, Zalatnai A, Comaru-Schally AM, Schally AV (1989) Membrane receptors for peptides in experimental and human pancreatic cancers. Pancreas 4:521–528
Finlay CA (1993) The mdm-2 oncogene can overcome wild type p53 suppression of transformed cell growth. Mol Cell Biol 13:301–306
Fölsch UR, Mustroph D, Schafmayer A, Becker HD, Creutzfeld W (1984) Elevated CCK plasma concentrations during acute and chronic feeding of soybean flour. Digestion 30:88
Fuji H, Egami H, Chaney W, Pour P, Pelling J (1990) Pancreatic ductal adenocarcinomas induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine contain a c-K-ras oncogene with a point-mutated codon 12. Mol Carcinog 3:296–301
Gao X, Honn KV, Grignon D, Sake W, Chen YQ (1993) Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas. Cancer Res 53:2723–2727
Goodrich DW, Wang NP, Qian YW, Lee EY, Lee WH (1991) The retinoblastoma gene product regulates progression through the Gl phase of the cell cycle. Cell 67:293–302
Greenblatt MS, Bennett WP, Hollsteins M, Harris CC (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855–4878
Hall PA, Lemoine NR (1992) Rapid acinar to ductal trans-differentiation in cultured human exocrine pancreas. J Pathol 166:97–103
Hedrick L, Cho KR, Fearon ER, Wu TC, Kinzler KW, Voglstein B (1994) The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes Dev 8:1174–1183
Hirayama T (1972) Smoking in relation to the death rates of 265,118 men and women in Japan. A report on five years of follow-up. Presented at the American Cancer Society’s 14th Science Writers Seminar. Clearwater Beach FL
Hohne MW, Halatch M-E, Kahl GF, Weinel RJ (1992) Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma. Cancer Res 52:2616–2619
Howe GR, Jain M, Miller AB (1990) Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study. Int J Cancer 45:604–608
Huang Y, Boynton RF, Blount PL, Silverstein RJ, Yin J, Tong Y, McDaniel TK, Newkirk C, Resau JH, Sridhara R, Reid BJ, Meltzer SJ (1992) Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. Cancer Res 52:6525–6530
Hubchak S, Mangino MM, Reddy MK, Scarpelli DG (1990) Characterization of differentiated Syrian golden hamster pancreatic duct cells maintained in extended monolayer culture. In Vitro Cell Dev Biol 26:889–897
Ide H, Subbarao V, Reddy JK, Rao MS (1993) Formation of ductular structures in vitro by pancreatic epithelial oval cells. Exp Cell Res 209:38–44
Ishikawa O, Ohigashi H, Imaoka S, Nakai I, Mitsuo M, Weide L, Pour P (1995) The role of pancreatic islers in experimental pancreatic carcinogenicity. Am J Pathol 147:1458–1464
Jhappan C, Staahle C, Harkins RN, Fausto N, Smith GH, Merlino GT (1990) TGFalpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61:1137–1146
Klijn JG, Hoff AM, Planting AS, Verweij J, Kok T, Lamberts SWJ, Portengen H, Foekens JA (1990) Treatment of patients with metastatic pancreatic and gastrointestinal tumours with the somatostatin analogue Sandostatin: a phase II study including endocrine effects. Br J Cancer 62:627–630
Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49
Leblond CP (1964) Classification of cell populations on the basis of their proliferative behavior. Natl Cancer Inst Monogr 14:119–150
Lee WH, Bookstein R, Hong F, Young LJ, Shew JY, Lee EY (1987) Human retinoblastoma susceptibility gene; cloning, identification and sequence. Science 235:1394–1399
Levine AJ (1993) The tumor suppressor genes. Annu Rev Biochem 62:623–651
Lhoste EF, Longnecker DS (1987) Effect of bombesin and caerulein on early stages of carcinogenesis induced by azaserine in the rat pancreas. Cancer Res 47:3273–3277
Lhoste EF, Roebuck BD, Longnecker DS (1988) Stimulation of the growth of azaserine-induced nodules in the rat pancreas by dietary camostate (FOY-305). Carcinogenesis 9:901–906
Longnecker DS (1991) Hormones and pancreatic cancer. Int J Pancreatol 9:81–86
Longnecker DS, Roebuck BD, Yager JD, Lilja HS, Siegmund B (1981) Pancreatic carcinoma in azaserine-treated rats, induction, classification and dietary modulation of incidence. Cancer 47:1562–1572
Longnecker DS, Faris RA, Bell RH Jr, Kuhlmann ET, Pettengill OS (1991) Ductal metaplasia in cell lines derived from an acinar cell carcinoma of the rat pancreas. Pancreas 6:710
Lu L, Louie D, Owyang CA (1989) A cholecystokinin releasing peptide mediates feedback regulation of pancreatic secretion. Am J Physiol 256:G430–G435
Makino T, Usuda N, Rao S, Reddy JK, Scarpelli DG (1990) Transdifferentiation of ductular cells into hepatocytes in regenerating hamster pancreas. Lab Invest 62:522–561
Matsukara N, Suzuki K, Kawochi T, Aoyai M, Sugimura T, Kitaoka H, Numajiri H, Shirota A, Itaboshi M, Hirota T (1980) Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation of complete and incomplete types of metaplasia to minute gastric carcinomas. J Natl Cancer Inst 65:231–240
McGuiness EE, Morgan RGH, Levison DA, Frape DL, Hopewood D, Wormsley KG (1980) The effects of long-term feeding of soya flour on the rat pancreas. Scand J Gastroenterol 15:497–502
McGuiness EE, Morgan RGH, Levison DA, Hopewood D, Wormsley KG (1981) Interaction of azaserine and raw soya flour on the rat pancreas. Scan J Gastroenterol 16:49–56
Meijers M, Bruijntjes JP, Hendriksen EG, Woutersen RA (1989) Histogenesis of early preneoplastic lesions induced by N-nitrosobis-(2-oxopropyl)amine in exocrine pancreas of hamsters. Int J Pancreatol 4:127–137
Meijers M, van Garderen-Hoetmer A, Lamers CB, Rovati LC, Jansen JBMJ, Woutersen RA (1990) Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. Carcinogenesis 11:2223–2226
Meijers M, Woutersen RA, van Garderen-Hoetmer A, Bakker GH, de Jong FH, Foekens JA, Klijn JG (1991) Effects of castration, alone and in combination with amino glutethimide, on growth of preneoplastic lesions in exocrine pancreas of rats and hamsters. Carcinogenesis 12:1707–1713
Meijers M, Appel MJ, van Garderen-Hoetmer A, Lamers CB, Rovati LC, Jansen JB, Woutersen RA (1992a) Effects of cholecystokinin and bombesin on development of azaserine-induced pancreatic tumours in rats: modulation by the cholecystokin receptor antagonist lorgiumide. Carcinogenesis 13:1525–1528
Meijers M, Visser CJ, Klijn JG, Lamberts SWJ, van Garderen-Hoetmer A, de Jong FH, Foekens JA, Woutersen RA (1992b) Effects of orchiectomy, alone or in combination with testosterone, and cyproterone acetate on exocrine pancreatic carcinogenesis in rats and hamsters. Int J Pancreatol 11:137–146
Miller DG (1980) On the nature of susceptibility to cancer. The presidential address. Cancer 46:1307–1318
Mills PK, Beeson WL, Abbey DE, Fraser GE, Phillips RL (1988) Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Cancer 61:2578–2585
Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245
Oates PS, Morgan RG (1982) Pancreatic growth and cell turnover in the rat fed raw soya flour. Am J Pathol 108:217–224
Okamura E, Okoda M, Onoda N, Kamiya Y, Murakami H, Tsuhima T, Shizume K (1990) Insulin-like growth factor I and transforming growth factor a as autocrine growth factors in human pancreatic cancer cell growth. Cancer Res 50:103–107
Parsa I, Longnecker DS, Scarpelli DG, Pour P, Reddy JK, Lefkowitz M (1985) Ductal metaplasia of human exocrine pancreas and its association with carcinoma. Cancer Res 45:1285–1290
Pour PM (1978) Islet cells as a component of pancreatic ductal neoplasms. 1. Experimental study: ductular cells including islet cell precursors and primary progenitor cells of tumors. Am J Pathol 90:295–316
Pour PM (1988) Mechanism of pseudoductular (tubular) formation during pancreatic carcinogenesis in the hamster model. An electron-microscopic and immune-histochemical study. Am J Pathol 130:335–344
Pour PM, Birt DF (1983) Modifying factors in pancreatic carcinogenesis in the hamster model. IV. Effects of dietary protein. J Natl Cancer Inst 71:347–353
Pour PM, Uchida E, Burnett DA, Steplewski Z (1986) Blood-group antigen expression during pancreatic cancer induction in hamsters. Int J Pancreatol 1:327–340
Pour PM, Lawson T, Hegelson S, Donnerly T, Stepan K (1988) Effect of cholecystokinin on pancreatic carcinogenesis in the hamster model. Carcinogenesis 9:597–601
Rao MS, Subbarao V, Reddy JK (1986) Induction of hepatocytes in the pancreas of copper-depleted rats following copper repletion. Cell Differ 18:109–117
Rao MS, Dwivedi RS, Subbarao V, Usman MI, Scarpelli DG, Nemali MR, Yeldandi A, Thangada S, Kumar S, Reddy JK (1988) Almost total conversion of pancreas to liver in the adult rat: a reliable model to study transdifferentiation. Biochem Biophys Res Commun 156:131–136
Rao MS, Yeldandi AV, Reddy JK (1990) Stem cell potential of ductular and periductular cells. Cell Differ Dev 29:155–163
Reddy BS, Sugie S (1988) Effect of different levels of omega-3 and omega-6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Res 48:6642–6647
Reddy JK, Kanwar YS, Rao MS, Watanabe TK, Reddy MK, Parsa I, Longnecker DS, Tafuri S (1986) Duct-like morphogenesis of Longnecker pancreatic acinar carcinoma cells maintained in vitro on seminiferous tubular basement membrane. Cancer Res 46:347–354
Reddy JK, Rao MS, Yeldandi AV, Tan X, Dwivedi RS (1991) Pancreatic hepatocytes. An in vivo model for cell lineage in pancreas of adult rat. Dig Dis Sci 36:502–509
Reubi JC, Horisberger U, Essed CE, Jeekel J, Klijn JG, Lamberts SWJ (1988) Absence of somatostatin receptors in human exocrine pancreatic adenocarcinomas. Gastroenterology 95:760–763
Rowlatt U (1967) Spontaneous epithelial tumours of the pancreas of mammals. Br J Cancer 21:82–107
Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brimster RL (1991) Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA 88:93–97
Scarpelli DG (1985) Editorial. Multipotent developmental capacity of cells in the adult animal. Lab Invest 52:331–333
Scarpelli DG, Rao MS (1981) Differentiation of regenerating pancreatic cells into hepatocyte-like cells. Proc Natl Acad Sci USA 78:2577–2581
Scarpelli DG, Rao MS, Reddy JK (1985) Experimental carcinogenesis of exocrine pancreas: animal models, neoplasms, and current understanding of pathogenesis. In: Jones TC, Mohr U, Hunt RD (eds) Digestive system. Springer, Berlin Heidelberg New York, pp 224–238
Scarpelli DG, Rao MS, Reddy JK (1991) Are acinar cells involved in the pathogenesis of ductal adenocarcinoma of the pancreas? Cancer Cells 3:275–277
Scemama JL, DeVries L, Pradayrol L, Seva C, Tronchere H, Vaysse N (1989) Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line. Am J Physiol 256:G846–G850
Schaeffer BK, Zurlo J, Longnecker DS (1990) Activation of c-K-ras not detectable in adenomas or adenocarcinomas arising in rat pancreas. Mol Carcinog 3:165–170
Scheck AC, Coons SW (1993) Expression of the tumor suppressor gene DCC in human gliomas. Cancer Res 53:5605–5609
Seymour AB, Hruban RH, Redston M, Caldas C, Powell SM, Kinzler KW, Yeo CJ, Kern SE (1994) Allelotype of pancreatic adenocarcinoma. Cancer Res 54:2761–2764
Shepherd JG, Chen JR, Tsao M-S, Duguid WP (1993) Neoplastic transformation of cultured rat pancreatic duct epithelial cells by azaserine and streptozotocin. Carcinogenesis 14:1027–1033
Shibata D, Almoguera C, Forrester K, Dunitz J, Martin SE, Cosgrove MM, Perucho M, Amheim N (1990) Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas. Cancer Res 50:1279–1283
Simon B, Weinel R, Hohne M, Watz U, Schmidt J, Kortner G, Arnold R (1994) Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma. Gastroenterology 106:1645–1651
Smith JJ, Derynck R, Korc M (1987) Production of transforming growth factor a in human pancreatic cancer cells: evidence for a superagonist autocrine cycle. Proc Natl Acad Sci USA 84:7567–7570
Sumi C, Longnecker DS, Roebuck BD, Brinck-Johnsen T (1989a) Inhibitory effects of estrogen and castration on the early stage of pancreatic carcinogenesis in Fischer rats treated with azaserine. Cancer Res 49:2332–2336
Sumi C, Brinck-Johnsen T, Longnecker DS (1989b) Inhibition of a transplantable pancreatic carcinoma by castration and estradial administration in rats. Cancer Res 49:6687–6692
Szende B, Srkalovic G, Serially AV, Lapis K, Groot K (1990a) Inhibitory effects of analogs of leutinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events which accompany tumor regression. Cancer 65:2279–2290
Szende B, Srkalovic G, Groot K, Lapis K, Serially AV (1990b) Regression of nitrosamine-induced pancreatic cancers in hamsters treated with luteinizing hormone-releasing hormone antagonists or agonists. Cancer Res 50:3716–3721
Townsend CM, Singh P, Thompson SC (1986) Gastrointestinal hormones and gastrointestinal and pancreatic carcinomas. Gastroenterology 91:1002–1006
Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, Kobayashi M, Sugimura T, Hirohashi (1992) Frequent loss of heterozygosity at the DCC locus in gastric cancer. Cancer Res 52:3099–3102
van Kranen HJ, Vermeuien E, Schoren L, Bax J, Woutersen RA, van Iersel P, van Kreije CF, Scherer E (1991) Activation of c-K-ras is frequent in pancreatic carcinomas of Syrian hamsters, but is absent in pancreatic tumors of rats. Carcinogenesis 12:1477–1482
Varley JM, Armour J, Swallow JE, Jeffrey AJ, Ponder BA, Walker RA (1989) Retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumors. Oncogene 4:725–729
Verma AK, Ashendel CL, Boutwell RK (1980) Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal orothine decarboxylase activity, the accumulation of prostaglandins, and tumor promotion caused by 12–0-tetradecanoylphorbol-13-acetate. Cancer Res 40:308–315
Woutersen RA, van Garderen-Hoetmer A, Longnecker DS (1987) Characterization of a 4-month protocol for the quantitation of BOP-induced lesions in hamster pancreas and its application in studying the effect of dietary fat. Carcinogenesis 8:833–837
Wynder EL (1975) An epidemiological evaluation of the causes of cancer of the pancreas. Cancer Res 35:2228–2233
Wynder EL (1976) Nutrition and cancer. Fed Proc 35:1309–1315
Wynder EL, Mabuchi K, Maruchi N, Former JG (1973) Epidemiology of cancer of the pancreas. J Natl Cancer Inst 50:645–667
Yoshida Y, Kaneko A, Chisaka N, Onoé T (1978) Appearance of intestinal type of tumor cells in hepatoma tissue induced by 3′-methyl-4-dimethylaminoazobenzene. Cancer Res 38:2753–2758
Zalatnai A, Serially AV (1989a) Treatment of N-nitrosobis(2-oxopropl)amine-induced pancreatic cancer in Syrian hamsters with D-Trp-6-LH-RH and somatostatin analog RC-160 microcapsules. Cancer Res 49:1810–1815
Zalatnai A, Serially A (1989b) Responsiveness of the hamster pancreatic cancer to treatment with microcapsules of D-Trp-6-LH-RH and somatostatin analog RC-160. Histological evidence of improvement. Int J Pancreatol 4:149–160
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Scarpelli, D.G. (1997). Experimental Carcinogenesis, Exocrine Pancreas, Hamster and Rat. In: Jones, T.C., Popp, J.A., Mohr, U. (eds) Digestive System. Monographs on Pathology of Laboratory Animals, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-25996-2_41
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