Summary
The present report is a study of the effect of the carcinogen nitrosomethylurea (NMU) on pancreas of rats receiving during lifetime a lipid-poor diet, that is essential fatty acid deficient or control diets. Rats fed a commercial stock chow were mated. At day 10 of pregnancy, dams were divided into three groups, that were respectively supplied with the commercial chow, the essential fatty acid deficient or the sufficient diet. Each litter was separated at random in two groups that received at day one of life one intraperitoneal injection of NMU (50 mg/kg b.w.) or saline. After weaning, they were maintained for life with the diet that was supplied to their mothers. The pancreas of NMU-treated rats presented diffuse proliferative changes, focal acinar cell hyperplasias (FACH), and focal hepatocyte-like metaplasia (FHLCM). FACH were expansive presumably preneoplastic growths, showing abnormal differentiation. The number of NMU-treated rats bearing FACH and FHLCM did not significantly differ in the three nutritional conditions.
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Abbreviations
- EFAD:
-
Essential fatty acid deficient diet
- EFAS:
-
Essential fatty acid sufficient diet
- FACH:
-
Focal acinar cell hyperplasia
- FHLCM:
-
Focal hepatocytee-like cell metaplasia
- NMU:
-
Nitrosomethylurea
- ST:
-
Stock diet
References
IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Some N-nitroso compounds, Lyon. 1978; 17: 227–255.
Leaver DD, Swann PF, Magee PN. The induction of tumors in the rat by a single oral dose of N-nitrosomethylurea. Br. J. Cancer 1969; 23: 177–187.
Terracini B, Testa MC. Carcinogenicity of a single administration of N-nkrosomethylurea: A comparison between newborn and 5-wk-old mice and rats. Br. J. Cancer 1970; 24: 588–598.
Monis B, Valentich MA, Urrutia R, et al.N-methyl-N-nitrosourea induces multicentric nodular adenomatous proliferation in rat pancreas which do not lead to malignant transformation. Proc. Am. Ass. Can. Res. 1989; 30: 116.
Hill EG, Johnson SB, Holman RT. Intensification of essential fatty acid deficiency in the rat by dietary trans fatty acids. J. Nutr. 1979; 109: 1759–1766.
Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 1957; 226: 497–507.
Morrison WR and Smith LM. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride methanol. J. Lip. Res. 1964; 5: 600–608.
Holman RT, Smythe L, Johnson S. Effect of sex and age on fatty acid composition of human serum lipds. Am. J. Clin. Nutr. 1979; 12: 2390–2399.
Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br. J. Cancer 1977; 35: 1–39.
Sokal RR, Rohlf FJ. Biometry (1969) Freeman WH and Company Ed., San Francisco and London.
Longnecker DS, Roebuck BD, Kuhlmann ET. Induction of pancreatic carcinomas in rats with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine. Histopathol. JNCI 1985; 74: 209–217.
Longnecker DS, Roebuck BD, Yager JD, et al. Pancreatic carcinoma in azaserine-treated rats: Induction, classification, and dietary modulation of incidence. Cancer 1981; 47: 1562–1572.
Duckery HS, Ivankovic D, Bucheler J, et al. Erzeugung von Magen-un Pancreas Krebs beim Meerschweinchen durchen durch Methyl-nitroso-harnstoff and -urethan. Z. Krebs-forschung 1968; 71: 167–182.
Reddy JK, Rao MS. Pancreatic adenocarcinoma in inbred guinea pigs induced by N-methyl-N-nitrosourea. Cancer Res. 1975; 35: 2269–2277.
Zimmerman JA, Trombetta LD, Carter TH, et al. Pancreatic carcinoma induced by NMU in aged mice. Gerontol. 1982; 20: 114–120.
Longnecker DS, Crawford BG. Hyperplastic nodules and adenomas of exocrine pancreas in azaserine-treated rats. JNCI 1974; 53: 573–577.
Konishi Y, Denda A, Inui S, et al. Pancreatic carcinoma induced by 4-hydroxyamino-quinoline 1-oxide after partial pancreatectomy and splenectomy in rats. Gann 1976; 67: 919–920.
Longnecker DS, Curphey TJ, Lilja HS, et al. Carcinogenicity in rats of the nitrosourea amino acid N-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO). J, Environ. Pathol. Toxicol. 1980; 4: 117–129.
Roebuck BD, Baumgartner KJ, Thron CD. Characterization of two populations of pancreatic atypical acinar cell foci induced by azaserine in the rat. Lab. Invest. 1984; 50: 141–146.
Konishi Y, Denda A, Miyata Y, et al. Enhancement of pancreatic tumorigenesis of 4-hydroxyaminoquinoline-1-oxide by ethionine in rats. Gann 1976; 67: 91–95.
Rao MS, Upton MP, Subbarao MS, et al. Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-hydroxyaminoquinoline-l-oxide in the rat pancreas. Lab. Invest. 1982; 46: 527–534.
Longnecker DS, Roebuck BD, Kuhlmann ET. Enhancement of pancreatic carcinogenesis by a dietary unsaturated fat in rats treated with saline of N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine. JNCI 1985; 74: 219–222.
Hruban Z, Swift H, Slesers A. Effect of azaserine on the fine structure of the liver and pancreatic acinar cells. Cancer Res. 1965; 25: 708–724.
Konishi Y, Popp JA, Shinozuka H. Pancreatic acinar cell damage induced by 4-nitro-quinoline 1-oxide and 4-hydroxyaminoquinoline. JNCI 1974; 52: 917–920.
Rivolta M, Urrutia R, Valentich MA, et al. Early changes induced by N-methyl-N-nitro-sourea in pancreas of rats fed on essential fatty acid deficient of sufficient diet. Com. Biol. 1988; 7: 123–133.
Pour PM, Runge RG, Birt D, et al. Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease. Cancer 1981; 47: 1573–1587.
Woutersen RA, van Gardener-HoetmerA, Bax J, et al. Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion. Carcinogenesis 1989; 10: 453–459.
Parsa I, Marsh WH, Sutton AL. An in vitro model of human pancreas carcinogenesis: Effects of nitroso compounds. Cancer 1981; 47: 1543–1551.
Reddy JK, Rao MS, Qureshi SA, et al. Induction and origin of hepatocytes in rat pancreas. J. Cell. Biol. 1984; 98: 2082–2090.
Hoover KL, Poirier LA. Hepatocyte-like cells within the pancreas of rats fed methyl-deficient diets. J. Nutr. 1986; 116: 1569–1575.
Roebuck BD, Yager JD, Longnecker DS. Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res 1981; 41: 888–893.
Roebuck BD, Yager JD, Longnecker DS, et al. Promotion by unsaturated fat of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res. 1981; 41: 3961–3966.
O’Connor TP, Roebuck BD, Campbell TC. Dietary intervention during the postdosing phase of L-azaserine-induced preneoplastic lesions. JNCI 1985; 75: 955–962.
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Mortis, B., Valentich, M.A., Urrutia, R. et al. Multicentric focal acinar cell hyperplasia and hepatocyte-like cell metaplasia are induced by nitrosomethylurea in rat pancreas. Int J Pancreatol 8, 119–131 (1991). https://doi.org/10.1007/BF02924426
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DOI: https://doi.org/10.1007/BF02924426