X radiation causes a persistent induction of reactive oxygen species and a delayed reinduction of TP53 in normal human diploid fibroblasts.
Multiple genetic changes are required for the development of a malignant cell. The frequency of such changes in cancer cells is higher than can be explained through random mutation, and it was proposed that a subpopulation of cells develop a persistent mutator phenotype. Evidence for such a phenotype has been observed in mammalian cells after treatment with ionizing radiation. The mechanism that promotes this effect has not been defined, but proposed explanations include increased levels of reactive oxygen species (ROS) in irradiated cells and their progeny. The tumor suppressor TP53 is of prime importance in coordinating the cellular response to damage, and it has been suggested to have a role in regulating the cellular redox state. We investigated the persistence of induced levels of ROS in normal diploid human cells for 1 month after X-ray exposure and the role of TP53 in this oxidant response. X radiation induced an oxidant response that persisted for 2 weeks after exposure in cells with normal TP53 function. ROS levels in cells with abrogated TP53 function were decreased in magnitude and duration. X radiation caused a primary transient induction of TP53 followed by a reinduction of TP53 5 days after irradiation. This reinduction persisted for at least 2 days and coincided with the largest induction of apoptosis. The persistently elevated levels of ROS and delayed reinduction of TP53 reported here are further evidence of the delayed effects of ionizing radiation and add to the growing number of such observations.
Rugo
R E
RE
Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.
Secretan
M B
MB
Schiestl
R H
RH
D000968:Antimycin A / Q000494:pharmacology; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D007700:Kinetics; D008168:Lung; D017382:Reactive Oxygen Species / Q000528:radiation effects*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects*; D014965:X-Rays
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D000968:Antimycin A