Gamma-irradiation-induced micronuclei from mouse hepatoma cells accumulate high levels of the tumor suppressor protein p53.

Abstract

The p53 tumor suppressor protein plays an important role in the G1 arrest of cells treated with DNA-damaging agents. Mouse hepatoma cells with wild-type or mutated p53 genotype were gamma-irradiated and the time course of p53 expression was determined by immunocytochemical staining. In p53 wild-type cells, gamma-irradiation led to a transient accumulation of the protein in the nuclei, whereas no such accumulation occurred in p53-mutated cells. Micronuclei were induced by gamma-irradiation in both wild-type and mutated cells in a dose- and time-dependent manner, but only micronuclei from p53 wild-type cells demonstrated a strongly positive staining reaction for p53 protein. This accumulation of p53 protein in micronuclei was not associated with a block in DNA synthesis as evidenced by bromodeoxyuridine labeling experiments.