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-Irradiation-induced Micronuclei from Mouse Hepatoma Cells Accumulate High Levels of the Tumor Suppressor Protein p53¹

German Cancer Research Center, Project Group Tumor Promotion in Liver, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany [C. U., S. K., M. S.], and Institute of Taxicology, University of Tübingen, 72074 Tübingen, Germany [A. B., M. S.]

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 -irradiated and the time course of p53 expression was determined by immunocytochemical staining. In p53 wild-type cells, -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 -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.

¹ Supported in part by the Deutsche Forschungsgemeinschaft.

² Present address: Department of Pharmacology and Toxicology, Purdue University, West-Lafayette, IN 47907-1334.

³ To whom requests for reprints should be addressed, at Institute of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany.

Received 3/15/94. Accepted 5/27/94.

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