Summary
Modifying effects of age, sex, and mouse strain on diethylnitrosamine (DEN) carcinogenesis have been investigated in C57BL/6Jx C3HeB/FeJ F1 (B6C3F1) and C3HeB/FeJxA/J F1 (C3AF1) hybrid mice. Animals each received four IP injections of 1.5 or 3.0 μg DEN/g body weight. The first injections were administered on days 1, 15, or 42 of life. Subsequent treatments were delivered at 3-, 6-, and 6-day intervals, respectively. Mice were kept under observation for the remaining life-span. DEN treatment induced tumors in liver, lungs, and forestomach in descending order of frequency. The majority of the induced liver tumors were hepatocellular carcinomas. Animals treated as newborns and infants developed significantly more liver tumors than animals that were treated as young adults. Newborn and infant females developed liver tumors at a later age (B6C3F1) and with a lower incidence (C3AF1) than similarly treated males. The B6C3F1 mice developed more hepatocellular carcinomas and a higher rate of pulmonary metastases than the C3AF1 mice. In contrast, C3AF1 mice developed lung tumors with a higher incidence and multiplicity than B6C3F1 hybrids. Forestomach tumors were observed also with a slightly but significantly higher incidence in C3AF1 mice.
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References
Bannasch P, Mayer D, Hacker HJ (1980) Hepatocellular glycogenosis and hepatocarcinogenesis. Biochim Biophys Acta 605:217–245
Cardesa A, Pour P, Althoff J (1974) Effects of intraperitoneal injections of dimethyl- and diethylnitrosamine, alone or simultaneously on Swiss mice. Z Krebsforsch 82:233–238
Clapp NK (1973) Carcinogenicity of nitrosamines and methanesulphonate esters given intraperitoneally in RF mice. Int J Cancer 27:728–733
Farber E (1980) The sequential analysis of liver cancer induction. Biochim Biophas Acta 605:149–166
Goldfarb S, Vesselinovitch SD, Pugh TD, Mihailovich N, Koen H, He Y (1980) Remarkable uniformity of premalignant and malignant hepatocellular foci after single dose injection of diethylnitrosamine (DEN) in infant mice. Gastroenterolgy 79:1021
Itze L, Vesselinovitch SD, Rao KVN (1975) Macromolecular turn-over in mouse (C57BLxC3H) liver, thymus, and kidney after partial hepatectomy. Physiol Bohemoslov 24:9–22
Kunz W, Schaude G, Schwarz M, Tennekes H (1982) Qualitative aspects of drug-mediated tumour promotion in liver and its toxicological implications. In: Hecker E, Fusenig N, Marks F, Kunz W (eds) Carcinogenesis, vol 7. Raven Press, New York, pp 111–125
Kyriazis P, Koka M, Vesselinovitch SD (1974) Metastatic rate of liver tumors induced by diethylnitrosamine in mice. Cancer Res 34:2881–2886
Lipsky MM, Hinton DE, Klaunig JE, Goldblatt PJ, Trump BF (1981a) Biology of hepatocellular neoplasia in the mouse. II. Sequential enzyme histochemical analysis of BALB/c mouse liver during safrole-induced carcinogenesis. JNCI 67:377–392
Lipsky MM, Hinton DE, Klaunig JE, Trump BF (1981b) Biology of hepatocellular neoplasia in the mouse. I. Histogenesis of safrole-induced hepatocellular carcinoma. JNCI 67:365–376
Moore MR, Drinkwater NR, Miller ED, Miller JA, Pitot HC (1981) Quantitative analysis of the time-dependent development of glucose-6-phosphatase-deficient foci in the livers of mice treated neonatally with diethylnitrosamine. Cancer Res 41:1585–1593
Peraino C, Fry RJM, Staffeldt E (1971) Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorence. Cancer Res 31:1506–1512
Peraino C, Fry RJM, Grube DD (1978) Drug-induced enhancement of hepatic tumorigenesis. In: Slaga TJ, Sivak A, Boutwell RK (eds) Carcinogenesis, mechanisms of promotion and cocarcinogenesis, vol 2. Raven Press, New York, pp 421–432
Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605:191–215
Rabes H, Szymkowiak R (1979) Cell kinetics of hepatocytes during the preneoplastic period of diethylnitrosamine-induced liver carcinogenesis. Cancer Res 39:1298–1304
Rao KVN, Vesselinovitch SD (1973) Age- and sex-associated diethylnitrosamine dealkylation activity of the mouse liver and hepatocarcinogenesis. Cancer Res 33:1625–1627
Scherer E, Emmelot P (1975a) Foci of altered liver cells induced by a single dose of diethylnitrosamine and partial hepatectomy: Their contribution to hepatocarcinogenesis in the rat. Eur J Cancer 11:145–154
Scherer E, Emmelot P (1975b) Kinetics of induction and growth of precancerous liver-cell foci and liver tumour formation by diethylnitrosamine in the rat. Eur J Cancer 11:689–696
Schmähl D, Thomas C (1965) Dosis-Wirkungs-Beziehungen bei der Erzeugung von Hämangioendotheliomen der Leber bei Mäusen durch Diäthylnitrosamin. Z Krebsforsch 66:533–535
Takayama S, Oota K (1965) Induction of malignant tumors in various strains of mice by oral administration of N-nitrosodimethylamine and N-nitrosodiethylamine. Gann 56:189–199
Turusov V, Tomatis L, Guibbert D, Duperray B, Pacheco H (1973) The effect of prenatal exposure of mice to methylcholanthrene combined with the neonatal administration of diethylnitrosamine. In: Tomatis L, Mohr N (eds) Transplacental carcinogenesis. International Agency for Research on Cancer, Lyons, pp 84–91
Vesselinovitch SD (1973) Comparative studies on perinatal carcinogenesis. In: Tomatis L, Mohr N (eds) Transplacental carcinogenesis. International Agency for Research on Cancer, Lyons, pp 14–22
Vesselinovitch SD, Mihailovich N (1967) The neonatal and infant age periods as biological factors which modify multicarcinogenesis by urethan. Cancer Res 27:1422–1429
Vesselinovitch SD, Mihailovich N (1983) Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res 43:4253–4259
Vesselinovitch SD, Mihailovich N, Wogan GN, Lombard LS, Rao KVN (1972) Aflatoxin B1, a hepatocarcinogen in the infant mouse. Cancer Res 32:2280–2291
Vesselinovitch SD, Rao KVN, Mihailovich N, Rice JM (1974) Development of broad spectrom of tumors by ethylnitrosourea in mice; modifying role of age, sex, and strain. Cancer Res 34:2530–2538
Vesselinovitch SD, Kyriazis AP, Mihailovich N, Rao KVN (1975a) Factors influencing augmentation and/or acceleration of lymphoreticular tumors in mice by benzo(a)pyrene. Cancer Res 35:1963–1969
Vesselinovitch SD, Kyriazis AP, Mihailovich N, Rao KVN (1975b) Conditions modifying development of tumors in mice at various sites by benzo(a)pyrene. Cancer Res 35:2948–2953
Vesselinovitch SD, Mihailovich N, Rao KVN (1978) Morphology and metastatic nature of induced hepatic nodular lesions in C57BLxC3H F1 mice. Cancer Res 38:2003–2010
Vesselinovitch SD, Rao KVN, Mihailovich N (1979) Neoplastic response of mouse tissues during perinatal age periods and its significance in chemical carcinogenesis. JNCI Monogr 51:239–250
Vesselinovitch SD, Itze L, Mihailovich N, Rao KVN (1980) Modifying role of partial hepatectomy and gonadectomy upon hepatocarcinogenesis by ethylnitrosourea. Cancer Res 40:1538–1542
Vesselinovitch SD, Mihailovich N, Rao KVN, Goldfarb S (1982) Relevance of basophilic foci to promoting effect of sex hormones on hepatocarcinogenesis. In: Hecker E, Fusenig N, Marks F, Kunz W (eds) Carcinogenesis, vol 7. Raven Press, New York, pp 127–131
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Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthday
These investigations have been supported in part by Contracts NIH-NCI-69-2087 and NO1-CO-43317 from the National Cancer Institute
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Vesselinovitch, S.D., Koka, M., Mihailovich, N. et al. Carcinogenicity of diethylnitrosamine in newborn, infant, and adult mice. J Cancer Res Clin Oncol 108, 60–65 (1984). https://doi.org/10.1007/BF00390974
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DOI: https://doi.org/10.1007/BF00390974