Abstract
The potential initiating activity of diethylnitrosamine (DEN) was studied in a rapid production model for pancreatic carcinogenesis in hamsters developed in our laboratory incorporating the principle of selection based on resistance to cytotoxicity, originally demonstrated for liver carcinogenesis in rats. Female Syrian golden hamsters were given DEN at a dose of 100 mg/kg body weight or N‐nitrosobis‐(2‐oxopropyI)amine (BOP) at a dose of 70 mg/kg body weight as initiators followed by 3 cycles of augmentation pressure (choline‐deficient diet combined with DL‐ethionine, L‐methionine upon return to basal diet and then administration of 20 mg/kg body weight BOP), and killed 10 weeks after the beginning of the experiment. DEN followed by the augmentation pressure induced a 65% incidence of total pancreatic lesions including 15% carcinomas, while BOP followed by the augmentation pressure induced 100% incidence of total pancreatic lesions and 84.2% for carcinomas. These yields were significantly greater than those observed for augmentation pressure alone. The results thus indicate that DEN possesses weak initiating activity for pancreatic carcinogenesis under the present experimental conditions.
Keywords: Diethylnitrosamine, Pancreatic carcinogenesis, Rapid production model, Hamster
Full Text
The Full Text of this article is available as a PDF (406.3 KB).
REFERENCES
- 1. ) Mizumoto , K. , Kitazawa , S. , Ito , S. , Takashima , S. , Tsutsumi , M. , Denda , A. and Konishi , Y.Cycles of repeated augmentation pressure in rapid production of pancreatic and cholangiocellular carcinomas in hamsters initiated with N‐nitrosobis(2‐oxopropyl)amine . Carcinogenesis , 10 , 1457 – 1459 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Mizumoto , K. , Tsutsumi , M. , Denda , A. and Konishi , Y.Rapid production of pancreatic carcinoma by initiation with N‐nitrosobis(2‐oxopropyl)amine and repeated augmentation pressure in hamsters . J. Natl. Cancer Inst. , 80 , 1564 – 1567 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Solt , D. and Farber , E.New principle for analysis of chemical carcinogenesis . Nature , 263 , 701 – 703 ( 1976. ). [Google Scholar]
- 4. ) Cayama , E. , Tsuda , H. , Sarma , D. S. R. and Farber , E.Initiation of chemical carcinogenesis requires cell proliferation . Nature , 275 , 60 – 62 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Leonard , T. B. , Dent , J. G. , Graichen , E. , Lyght , O. and Popp , J. A.Comparison of hepatic carcinogen initiation‐promotion systems . Carcinogenesis , 3 , 851 – 856 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Tatematsu , M. , Hasegawa , R. , Imaida , K. , Tsuda , H. and Ito , N.Survey of various chemicals for initiating and promoting activities in a short‐term in‐vivo system based on generation of hyperplastic liver nodules in rats . Carcinogenesis , 4 , 381 – 386 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Pilot , H. C. , Barsness , L. and Goldsworthy , T.Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine . Nature , 271 , 456 – 458 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Vesselinovitch , S. D. and Mihailovich , N.Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse . Cancer Res. , 43 , 4256 – 4259 ( 1983. ). [PubMed] [Google Scholar]
- 9. ) Takayama , S. and Oota , K.Induction of malignant tumors in various strains of mice by oral administration of N‐nitrosodimethylamine and N‐nitrosodiethy amine . Gann , 56 , 189 – 199 ( 1965. ). [PubMed] [Google Scholar]
- 10. ) Vesselinovitch , S. D. , Mihailovich , N. and Rao , K. V. N.Morphology and metastatic nature of induced hepatic nodular lesions in C57BLXC3H F1 mice . Cancer Res. , 38 , 2003 – 2010 ( 1978. ). [PubMed] [Google Scholar]
- 11. ) Herrold , K. M. and Dunham , L.Induction of tumors in the Syrian golden hamster with diethylnitrosamine (N‐nitrosodiethylamine) . Cancer Res. , 23 , 773 – 777 ( 1963. ). [PubMed] [Google Scholar]
- 12. ) Montesano , R. and Saffiotti , U.Carcinogenic response of the respiratory tract of Syrian golden hamsters to different doses of diethylnitrosamine . Cancer Res. , 28 , 2197 – 2210 ( 1968. ). [PubMed] [Google Scholar]
- 13. ) Parsa , L , Marsh , W. H. and Sutton , A. L.An in vitro model of human pancreas carcinogenesis: effect of nitroso compounds . Cancer , 47 , 1543 – 1551 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Pour , P. M. and Wilson , R. B.Experimental tumors of the pancreas . In“Tumors of the Pancreas ”, ed. Moosa A. R. , pp. 37 – 58 ( 1980. ). Williams and Wilkins; , Baltimore . [Google Scholar]
- 15. ) Kozuka , S. , Sassa , R. , Taki , T. , Masamoto , K. , Nagasawa , S. , Saga , S. , Hasegawa , K. and Takeuchi , M.Relation of pancreatic duct hyperplasia to carcinoma . Cancer , 43 , 1418 – 1428 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Bannasch , P. , Benner , H. and Zerban , H.Cholangiofibroma and cholangipcarcinomas . In “ Digestive System ”, ed. Jones T. C. , Mohr U. and Hunt R. D. , pp. 52 – 65 ( 1985. ). Springer‐Verlag; , Berlin . [Google Scholar]
- 17. ) Columbano , A. , Rajalakshmi , S. and Sarma , D. S. R.Requirement of cell proliferation for the initiation of liver carcinogenesis as assayed by three different procedures . Cancer Res. , 41 , 2079 – 2083 ( 1981. ). [PubMed] [Google Scholar]
- 18. ) Parsa , I. and Marsh , W. H.An in vitro model of pancreatic carcinoma ‐ morphology and in vivo growth . Am. J. Pathol. , 84 , 469 – 478 ( 1976. ). [PMC free article] [PubMed] [Google Scholar]
- 19. ) Groenen , P. J. , Jonk , R. J. , van Ingen , C. and ten Noever de Brauw , M. C.Determination of eight volatile nitrosamines in thirty cured meat products with capillary gas chromatography‐high‐resolution mass spectrometry: the presence of nitrosodiethylamine and the absence of nitrosopyrrolidine . IARC Sci. Publ. , 14 , 321 – 331 ( 1976. ). [PubMed] [Google Scholar]
- 20. ) Mirvish , S. S.Formation of N‐nitroso compounds: chemistry, kinetics and in vivo occurrence . Toxicol. Appl. Pharmacoi. , 31 , 325 – 351 ( 1975. ). [DOI] [PubMed] [Google Scholar]
