Effect of Age at Treatment on Incidence and Type of Renal Neoplasm Induced in the Rat by a Single Dose of Dimethylnitrosamine

The effect of age at treatment on the incidence and type of kidney tumor induced by dimethylnitrosamine was investigated in an established model of experimental renal carcinogenesis. Groups of Porton albino Wistar rats were dosed with carcinogen at 24 hr; at 3 weeks; and at 1, 1.5, 2, 3, 4, and 5 months of age. In all groups except the neonates, the animals were preconditioned by feeding a no-protein, high-carbohydrate diet for 5 days prior to the i.p. injection of dimethylnitrosamine (30 mg/kg). In the neonatal group, it was necessary to reduce the dose of carcinogen to 20 mg/kg in order to achieve approximately equivalent numbers of survivors. Notwithstanding the loss of strict comparability of data between the newborns and the remaining age groups, kidney tumor incidence showed a bimodal distribution represented by the occurrence of two separate entities, renal mesenchymal tumor and cortical epithelial tumor. Mesenchymal tumor proved to be a neoplasm of the neonatal and immature rat, the susceptibility to which fell rapidly after one month of age to nil at five months of age. In contrast, susceptibility to tumors of cortical tubule epithelium increased with ensuing sexual maturity, but it declined by five months of age. Age at dosing also influenced to some degree the grade of tumor induced. An altered grade of mesenchymal tumor was illustrated by the emergence in older age groups of a fibroma-like variant not encountered in earlier groups while epithelial tumors graded as carcinoma were not induced in rats dosed at five months of age. The adenomas in this group also presented a less active appearance than did equivalent lesions in earlier groups. No neoplasms conforming to the classification of renal lipomatous tumor were among the one hundred mesenchymal neoplasms induced in this study, but a single lesion consistent with an early nephroblastoma was found in one rat dosed at birth. The exclusive occurrence of two predominant types of kidney tumor emphasizes once again the specificity of the host-tumor interaction elicited by dimethylnitrosamine.