DNA-dependent protein kinase does not play a role in adaptive survival responses to ionizing radiation

Environmental Health Perspectives
E OdegaardD A Boothman

Abstract

We previously demonstrated that exposure of certain human tumor cells to very low chronic doses of ionizing radiation led to their enhanced survival following exposure to subsequent high doses of radiation. Survival enhancement due to these adaptive survival responses (ASRs) ranged from 1.5-fold to 2.2-fold in many human tumor cells. Furthermore, we showed that ASRs result from altered G1 checkpoint regulation, possibly mediated by overexpression of cyclin D1, proliferating cell nuclear antigen (PCNA), and the X-ray induction of cyclin A. Because cyclin D1 and PCNA proteins are components of many DNA synthetic and repair processes in the cell, we tested the hypothesis that preexposure of cells to low doses of ionizing radiation enabled activation of the DNA repair machinery needed for survival recovery after high-dose radiation. We examined the role of DNA break repair in ASRs using murine cells deficient (i.e., severe combined immunodeficiency [SCID] cells) or proficient (i.e., parental mouse strain [CB-17] cells) in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression and DNA double-strand break repair, DNA-PKcs is a nuclear serine/threonine protein kinase that is activated by DNA breaks and plays a key role i...Continue Reading

References

Feb 1, 1992·Mutation Research·J D Shadley, G Q Dai
Jul 2, 1992·Nature·D P Lane
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D A Boothman, A B Pardee
Dec 1, 1995·The Journal of Experimental Medicine·L A Casciola-RosenA Rosen
Jan 1, 1997·Apoptosis : an International Journal on Programmed Cell Death·M P Mattson, K Furukawa

❮ Previous
Next ❯

Citations

Dec 6, 2008·Cancer Letters·Delphine T Marie-EgyptienneChantal Autexier
Oct 2, 1998·Human & Experimental Toxicology·D A BoothmanM S Mendonca
Apr 24, 1999·Biochimie·F Eckardt-Schupp, C Klaus
Jul 11, 2002·Mutation Research·Masao S SasakiTaisei Nomura

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.