Abstract

Following discovery that the type of kidney neoplasm in-duced in protein-deprived Wlstar rats by a single dose of dimethylnitrosamine (DMN) was age-dependent, this study aimed to refine the system In order to develop a high fre-quency model for the induction of cortical epithelial tumors with low mesencfaymal tumor incidence. Using outbred fe-male Crl:(W)BR (Charles River Wlstar) rats, DMN at a dose of 30 mg/kg was administered at 9- 1 0 weeks of age follow-ing a 5-day period of high-carbohydrate/no-protein diet. From a total of 49 rats, 43 survived the early toxkdty and 91% of these developed renal tumors. Mesenchymal tumors were present in only 9 % of the tumor-bearing animals, in contrast, 70 % of the rats developed epithelial tumors of the tubules classifiable on a size and hlstological basis as adenocard-nomas/cardnomas hi response to DMN. A further 21 % of rats had smaller proliferative lesions designated as adenomas, making the total cortical epithelial tumor incidence hi excess of 90%. The malignant potential of the epithelial tumors was underscored by the presence of metastatic invasion, mainly involving the lungs, in 15 % of the tumor-bearing rats. Meta-statfc behavior correlated with progressive growth of the car-dnomas over a period of time exceeding 1.5 years to dimen-sions usually exceeding 2.9 cm diameter. Of the tumors approaching or exceeding this size, the metastatic rate was almost 50%. Thus, the administration of DMN to 65-70 days old, protein-deprived Wlstar rats provides a potent, single dose model for the study of renal epithelial cardnogen-esis with insignificant mesenchymal tumor induction and without the continuing toxidty which perturbs regimens based on repeated or continuous exposures.