Use of the spontaneous Tsc2 knockout (Eker) rat model of hereditary renal cell carcinoma for the study of renal carcinogens.

The kidney is a frequent site for chemically induced cancers in rodents and among the 10 most frequent sites for cancer in human patients. Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Hereditary RCC occurs in Eker rats that are heterozygous for an insertion mutation in the Tsc2 tumor suppressor gene. The germline mutation renders heterozygous mutants highly susceptible to renal carcinogens. The utility of this model in studying potential renal carcinogens is due to an ordered progression of proliferative renal lesions that can be identified and counted microscopically. The quantitative nature of the model allows for the production of statistically powerful data to understand the relative degree and potency of chemical effects and allow analysis of genetic alterations that may be chemical specific.