Screening for p53 mutations in C3H/He mouse liver tumors derived spontaneously or induced with diethylnitrosamine or...

Distinct differences have been described in the development of C3H/He mouse liver tumors induced by the genotoxic carcinogen diethylnitrosamine (DEN) and by the nongenotoxic agent phenobarbitone (PB) in terms of pathology and the frequency of mutation at codon 61 of the Ha-ras oncogene. To further define the mechanisms involved, we screened the tumor suppressor gene p53 for mutations in exons 5, 7, and 8 using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Nearly all the mutations so far described have been found within these three exons. In this study a total of six spontaneous tumors, eight tumors induced by PB, 14 tumors induced by DEN, and five samples of normal liver tissue were screened, and no mutations were found in any of the tumors examined. The positive control, the plasmid LTRp53cG (val), had a point mutation in exon 5 that was detected by PCR-SSCP. Since many of the tumors were late-stage hepatocellular carcinomas, we concluded that mutations in exons 5, 7, and 8 of the p53 gene do not play an important role in the development of chemically induced liver tumors in the C3H/He mouse.