p53 status in spontaneous and dimethylnitrosamine-induced renal cell tumors from rats.
Rats carrying the Eker tumor-susceptibility mutation (Eker rats) are predisposed to developing renal cell carcinoma. Rats heterozygous for the Eker mutation develop spontaneous multiple bilateral renal cell tumors by the age of 1 yr. In a previous study, Eker-mutation carrier and noncarrier rats were exposed to the renal carcinogen dimethylnitrosamine (DMN), and male rats carrying the Eker mutation exhibited a 70-fold increase in the induction of renal adenomas and carcinomas when compared with noncarrier rats. In this study, spontaneous and DMN-induced rat renal cell tumors (adenomas and carcinomas) were analyzed for mutations of the p53 gene by direct sequencing of cDNA polymerase chain reaction products. There were no mutations in p53 cDNA derived from renal tumors from six untreated rats. Mutations were found in one of 15 of the DMN-induced tumors: a transition at codon 140, CCT-->CTT, in a renal adenoma. Additionally, seven cell lines derived from spontaneous renal cell tumors did not contain mutations in p53. The low frequency of p53 mutations (one of 21 renal cell tumors and none of seven cell lines derived from renal cell tumors) indicates that the development of both spontaneous and carcinogen-induced renal tumors involved a non-p53-dependent pathway. As p53 is infrequently mutated in human renal cell carcinomas and in rat renal mesenchymal tumors, it is likely that a tumor suppressor gene or genes other than p53 are involved in the development of renal cancer.
Horesovsky
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Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA.
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Everitt
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Goldsworthy
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Wolf
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Walker
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D000236:Adenoma / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000235:genetics*; D002460:Cell Line; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics*; D004128:Dimethylnitrosamine; D016158:Genes, p53; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics*; D017354:Point Mutation; D051381:Rats; D011919:Rats, Inbred Strains
D003062:Codon; D004273:DNA, Neoplasm; D004128:Dimethylnitrosamine