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© 1995 Oxford University Press

research-article

Effect of stage of development on frequency and pathogenesis of kidney tumors induced in Noble (Nb) rats exposed prenatally or neonatally to N-nitrosoethylurea

Bhalchandra A. Diwan 3 and Jerry M. Rice 1 2

Biological Carcinogenesis and Development Program SAIC Frederick
1Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center Frederick, MD 21702, USA
2Present address: Office of the Associate Director, NCI-Fredenck Cancer Research and Development Center, Frederick, MD 21702, USA

3To whom correspondence should be addressed

Wilms' tumor of kidney, a common human childhood neoplasm, is modeled by nephroblastomas induced by prenatal exposure of some rodents to alkylating agents. Noble (Nb) rats are especially susceptible. We studied the ontogeny of susceptibility by treatment with N-nitrosoethyl-urea (NEU) on gestation day 10, 12, 14, 16 or 18 or neonatal day 1, 3, 5, 7 or 10. No nephroblastomas were observed in offspring exposed to NEU on day 10 or 12 of gestation. In contrast, nephroblastomas commonly occurred in rats exposed on gestation day 14,16 or 18 of gestation, with the highest incidence (48%) after treatment on day 18. Nephroblastomas were rare (<10%), but renal mesenchymal tumors were common (25–30%) in rats exposed to NEU on day 1 or 3 after birth. In rats exposed to NEU on day 7 or 10 only renal mesenchymal tumors were seen. Thus our results suggest that the stage of differentiation of fetal and neonatal kidneys at the time of NEU administration determines the frequency and type of kidney tumors induced in Nb rats. Since NEU induces both nephroblastomas and mesenchymal tumors in this strain, this experimental model may prove useful for the study of molecular mechanisms involved in the development of these two histogenetically different types of kidney tumors.


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