Genetic predisposition to transplacentally induced renal cell carcinomas in the Eker rat.

Abstract

N-Ethyl-N-nitrosourea-induced transplacental renal carcinogenesis in the rat results primarily in Wilms' tumors, apparently because primitive nephroblasts are the preferred target. Our question is whether N-ethyl-N-nitrosourea-induced mutations in the fetal kidney would increase the number of adult-type renal cell carcinomas in the Eker rat, which is heterozygous for a mutation that predisposes to renal cell carcinoma. Surprisingly, renal cell tumors but no Wilm's tumors began to appear from as early as 1 week after birth. Thus, the inheritance of a renal cell carcinoma mutation determines the specificity of tumor histology even with in utero carcinogenesis.