Modulation and cell cycle distribution of mutant p53 protein in a human small-cell lung carcinoma cell line after exposure to cytotoxic agents

Changes in the level and in the cell cycle distribution of a mutant p53 protein were investigated in a human small-cell lung carcinoma cell line after treatment with ionizing radiation or DNA-damaging antitumor drugs. This cell line was selected because it was found to be monosomic for chromosome 17, to carry a p53 gene mutated at codon 245 (resulting in the amino acid substitution Gly > Asp), and to be resistant to ionizing radiation. The DNA damaging agents etoposide,, cis-diamminedicholoroplatinum, or camptothecin induced a time- and dose-dependent increase in mutant p53 protein levels in all the phases of the cell cycle, although most of the cells were arrested in the G2 phase. Colcemid blocked cells in G2+M phases with a small but consistent effect on p53 protein levels. Exposure to gamma-rays induced changes in p53 levels 1 h after irradiation, when no effects on the cell cycle were evident, and at 24 h, when cells were arrested in the G2, although a significant fraction of cells was still present in the G1 phase. These findings indicate that, although enhancement of p53 might be related to cell accumulation in G2+M phases (where levels are higher than in G1, or in S phase), genotoxic lesions modulated levels of mutant p53 protein in all the phases of the cell cycle.