Differential renal tumor response to N-ethylnitrosourea and dimethylnitrosamine in the Nb rat: basis for a new rodent model of nephroblastoma.

Abstract

Previous studies have indicated that the Nb rat has a higher predisposition to the spontaneous development of nephroblastoma than most other strains of laboratory rat. In order to determine whether this inherent susceptibility could be exploited as a model for Wilms' tumor, Nb rats were treated with various chemicals in regimens known to be associated with renal tumor induction in the young rat. Nb rats were either exposed in utero to various dose levels of N-ethylnitrosourea (ENU) on day 18 +/- 1 of gestation, injected s.c. with one 25 mg/kg dose of dimethylnitrosamine (DMN) as neonates or dosed twice orally with 7,12-dimethylbenz[a]anthracene (DMBA) shortly after ovariectomy. Transplancental ENU at a dose of 60 mg/kg resulted in an average of 50% frequency of unequivocal nephroblastomas in both sexes with no renal mesenchymal tumors. In contrast, DMN administered to neonates produced a similar incidence of renal mesenchymal tumors but no nephroblastomas. DMBA in the ovariectomized female was not a successful strategy for inducing primary renal tumors in the Nb rat (0 nephroblastomas, 1 renal mesenchymal tumor in 16 effective survivors), although the kidney was sometimes the site for metastatic invasion by tumors originating at other locations. The induction of nephroblastomas and renal mesenchymal tumors by ENU and DMN in parallel experiments emphasized the many differences which establish them as distinct and unrelated tumor entities. The relatively high incidence of nephroblastoma in the Nb rat using transplacentally administered ENU appears to represent a suitable basis for developing a rodent model of human nephroblastoma or Wilms' tumor.