Indistinct cell cycle checkpoint after u.v. damage in H-ras-transformed mouse liver cells despite normal p53 gene...

Growth arrest after u.v. damage was investigated in C3H mouse primary cultured hepatocytes, spontaneously immortalized liver epithelial cells and their H-ras-transformed derivatives. All cells except for one of the transformed lines had the wild type p53 gene considered necessary for the G1-S checkpoint. Growth arrest and accumulation of p53 protein with an abnormally-extended half-life were observed after 8 J/m2 u.v. treatment in primary hepatocytes and immortalized cells, but the arrest was much less evident in H-ras-transformed cells, in spite of the presence of the wild type p53 gene and accumulation of p53. Thus, the signal transduction upstream of p53 in the p53-mediated G1-S checkpoint may be retained in these transformed cell lines, although its downstream signal transduction or a pathway totally independent of this system could be altered. The transformed cells showed a much wider distribution of chromosomal number as compared to normal and immortalized cells, indicating that progression from the immortal to transformed state is associated with chromosomal instability, together with much decrease in the cell cycle checkpoint function.