p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis.

Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (Gl) tract, a condition called the Gl syndrome. Whether the target cells affected by radiation to cause the Gl syndrome are derived from the epithelium or endothelium and whether the target cells die by apoptosis or other mechanisms are controversial issues. Studying mouse models, we found that selective deletion of the proapoptotic genes Bak1 and Bax from the Gl epithelium or from endothelial cells did not protect mice from developing the Gl syndrome after sub-total-body gamma irradiation. In contrast, selective deletion of p53 from the Gl epithelium, but not from endothelial cells, sensitized irradiated mice to the Gl syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the Gl syndrome after irradiation. These results suggest that the Gl syndrome is caused by the death of Gl epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis. [ABSTRACT FROM AUTHOR]