LACK OF P53 POINT MUTATIONS IN CHEMICALLY-INDUCED MOUSE HEPATOBLASTOMAS - AN END-STAGE, HIGHLY MALIGNANT HEPATOCELLULAR TUMOR

Inactivation of the p53 tumor suppressor gene appears to be an importa nt event in the progression of many types of human neoplasms; however its role in rodent experimental tumorigenesis is controversial. Previo us studies have shown that a wide array of chemically induced and spon taneous mouse liver tumors lack p53 mutations within the evolutionaril y conserved regions of exons 5-8. However, since p53 inactivation in h uman neoplasms occurs relatively late in tumor progression, it is poss ible that the mouse liver tumors evaluated previously were not suitabl y advanced to incur p53 aberrations. In the present study, we examined an end-stage, highly malignant embryonal mouse liver tumor known as t he hepatoblastoma (HB) for p53 mutations utilizing the highly sensitiv e 'cold' single-strand conformation polymorphism (SSCP) technique. In addition, several of the HBs were examined by direct nucleotide sequen cing. No aberrations of the p53 gene were detected within exons 5-8 of any of the 16 HBs examined. These results confirm that the p53 gene p lays a minimal role in the development or malignant progression of hep atocellular tumors in mice.