Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice.
Document Type
Article
Publication Date
2004
Keywords
Digestive-System, Hematopoiesis, Mice, Mice-Inbred-C57BL, Protein-p53, Radiation-Tolerance, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Thiazoles, Toluene
First Page
3265
Last Page
3271
JAX Source
Oncogene 2004 Apr; 23(19):3265-71.
Abstract
Ionizing radiation (IR) induces p53-dependent apoptosis in radiosensitive tissues, suggesting that p53 is a determinant of radiation syndromes. In fact, p53-deficient mice survive doses of IR that cause lethal hematopoietic syndrome in wild-type animals. Surprisingly, p53 deficiency results in sensitization of mice to higher doses of IR, causing lethal gastro-intestinal (GI) syndrome. While cells in the crypts of p53-wild-type epithelium undergo prolonged growth arrest after irradiation, continuous cell proliferation ongoing in p53-deficient epithelium correlates with accelerated death of damaged cells followed by rapid destruction of villi and accelerated lethality. p21-deficient mice are also characterized by increased sensitivity to GI syndrome-inducing doses of IR. We conclude that p53/p21-mediated growth arrest plays a protective role in the epithelium of small intestine after severe doses of IR. Pharmacological inhibition of p53 by a small molecule that can rescue from lethal hematopoietic syndrome has no effect on the lethality from gastro-intestinal syndrome, presumably because of a temporary and reversible nature of its action.
Recommended Citation
Komarova EA,
Kondratov RV,
Wang K,
Christov K,
Golovkina TV,
Goldblum JR,
Gudkov AV.
Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene 2004 Apr; 23(19):3265-71.