Abstract
Syrian golden hamsters have a very short period (15 days) of gestation. The implantation of the balstocyst occurs on day 5, embryogenesis proceeds very rapidly thereafter and neural tube closure is completed by day 9. In the present study the effects of two different doses ofN-nitrosoethylurea (NEU) administered at various stages of gestation were quantitatively evaluated in Syrian golden hamsters. NEU at either 0.2 or 0.5 mmol/kg was administered transplacentally as a single i.p. injection to pregnant hamsters on gestation days 7, 8, 9, 10, 11, 12, 13, or 14. The incidence, latency period and multiplicity of tumors varied with the dose of NEU and the stage of development at the time of NEU administration. Although tumors of the peripheral nervous system predominated, a variety of other tumors, including melanomas and visceral tumors of epithelial and mesenchymal origin, were also observed in hamster offspring exposed transplacentally to NEU. Sensitivity to transplacental carcinogenesis was maximal during late gestation and very low before day 9.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- NEU :
-
N-nitrosoethylurea
- PNS:
-
peripheral nervous system
- CNS :
-
central nervous system
References
Boyer CC (1968) Embryology. In: Hoffman RA, Robinson PF, Magalhues H (eds) The golden hamster, its biology and use in medical research. The Iowa State University Press, Ames, Iowa, pp 73–89
Cardesa A, Rustia M, Mohr U (1982) Tumours of the nervous system. In: Turusov VS (ed) Pathology of tumours in laboratory animals, vol III. Tumours of the hamster. International Agency for Research on Cancer, Lyon, pp 413–436
Diwan BA, Meier H (1974) Strain-and age-dependent transplacental carcinogenesis by 1-ethyl-1-nitrosourea in inbred strains of mice. Cancer Res 34: 764–770
Druckrey H, Ivankovic S, Preussmann R (1966) Teratogenic and carcinogenic effects in the offspring after single injection of ethylnitrosourea to pregnant rats. Nature 210: 1378–1379
Ernst M, Rittinghausen S, Wahnschaffe U, Mohr U (1987) Induction of malignant peripheral nerve sheath tumors in European hamsters with 1,1-dimethyl-hydrazine. Cancer Lett 35: 303–311
Fox RR, Diwan BA, Meier H (1975) Transplacental induction of primary renal tumors in rabbits treated with 1-ethyl-1-nitrosourea. J Natl Cancer Inst 54: 1439–1448
Givelber HM, DiPaolo JA (1969) Teratogenic effects ofN-ethyl-N-nitrosourea in the Syrian hamster. Cancer Res 29: 1151–1155
Gold E, Gordis L, Tonascia J, Szklo M (1979) Risk factors for brain tumors in children. Am J Epidemiol 109: 309–319
Grufferman S, Wang HH, Delong ER, Kimm SYS, Delzell ES, Falleta JM (1982) Environmental factors in the etiology of rhabdomyosarcoma in childhood. J Natl Cancer Inst 68: 107–113
Ivankovic S (1979) Teratogenic and carcinogenic effects of some chemicals during prenatal life in rats, Syrian golden hamsters, and minipigs. NCI Monogr 51: 103–115
Ivankovic S, Druckrey H (1968) Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Äthylnitrosoharnstoff (ANH) an BD IX-Ratten. Z Krebsforsch 71: 320–360
Kleihues P, Rajewsky MF (1984) Chemical neuro-oncogenesis: role of structural DNA modifications, DNA repair and neural target cell population. Prog Exp Tumor Res 27: 1–6
Kleihues P, Volk B, Kovacs G, Kuehnl-Petzoldt C (1985) Development and biology of ethylnitrosourea-induced melanomas in the Mongolian gerbil (Meriones unguiculatus). In: Bagnara J, Klaus SN, Paul E, Schartl M (eds) Biochemical, molecular and clinical aspects of pigmentation. University of Tokyo Press, Tokyo, Japan, pp 465–470
Kramer S, Ward E, Meadows AT, Malone KE (1987) Medical and drug risk factors associated with neuroblastoma: a case-control study. J Natl Cancer Inst 78: 797–804
Mennel ME, Zülch KJ (1972) Zur Morphologie transplacentar erzeugener Tumoren beim Goldhamster. Acta Neuropathol 21: 194–203
Nakamura T, Hara M, Kasaga T (1989) Transplacental induction of peripheral nervous tumor in the Syrian golden hamster byN-nitroso-N-ethylurea. Am J Pathol 135: 251–259
Nakamura T, Hara M, Kasuga T (1991) Early lesion ofN-nitroso-N-ethylurea-induced hamster neurofibromatosis model. Cancer Res 51: 434–438
Nemato T, Nakamura T, Ohashi K, Kasuga T (1993)N-Nitroso-N-ethylurea-induced hamster melanoma: a new method for efficient induction and Schwannian differentiation of melanoma. Jpn J Cancer Res 84: 512–517
Perantoni AO, Rice JM, Reed CD, Watatani M, Wenk ML (1987) Activatedneu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea. Proc Natl Acad Sci USA 84: 6317–6321
Preston-Martin S, Yu MC, Benton B, Henderson BE (1982)N-Nitroso compounds and childhood brain tumors: a case-control study. Cancer Res 42: 5240–5245
Rice JM (1969) Transplacental carcinogenesis in mice by 1-ethyl-1-nitrosourea. Ann NY Acad Sci 163: 813–826
Rice JM (1973) An overview of transplacental chemical carcinogenesis. Teratology 8: 113–126
Rice JM (1981) Effects of prenatal exposure to chemical carcinogens and methods for their detection. In: Kimmel CA, Buelke-Sam J (eds) Developmental toxicology. Raven, New York, pp 191–211
Rice JM, Ward JM (1982) Age dependence of susceptibility to carcinogenesis in the nervous system. Ann NY Acad Sci 381: 274–289
Rustia M (1976) Effect of gonadal ablation on transplacentally induced neurogenic tumors in hamsters. Cancer Res 36: 240–245
Rustia M, Schenken J (1976) Transplacental effects of ethylnitrosourea precursors ethylurea and sodium nitrite in hamsters. Z Krebsforsch 85: 201–217
Rustia M, Shubik P (1973) Transplacental carcinogenesis in hamsters. Proc Am Assoc Cancer Res 14: 81
Rustia M, Shubik P (1974) Prenatal induction of neurogenic tumors in hamsters by precursors ethylurea and sodium nitrite. J Natl Cancer Inst 52: 605–608
Shepard TH (1980) Catalog of teratogenic agents, 3rd edn. Johns Hopkins University Press, Baltimore, Md.
Stavrou D, Dahme E, Haenichen T (1984) Transplacental carcinogenesis in the rabbit. In: Schuller HM (ed) Comparative transplacental carcinogenesis. CRC Press, Boca Raton, Fl, pp 23–43
Vesselinovitch SD, Koka M, Rao KVN, Mihailovich N, Rice JM (1977) Prenatal carcinogenesis by ethylnitrosourea in mice. Cancer Res 37: 1822–1828
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Diwan, B.A., Rehm, S. & Rice, J.M. Age- and dose-dependent transplacental carcinogenesis byN-nitrosoethylurea in Syrian golden hamsters. J Cancer Res Clin Oncol 122, 643–652 (1996). https://doi.org/10.1007/BF01209026
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01209026