| Induced radioresistance in four strains of Escherichia coli, two with lambda lysogens Biophysical Journal, Volume 22, Issue 3, 1 June 1978, Pages 431-438 E.C. Pollard Abstract Cells of E. coli that are recA+ and lex+ show a phenomenon of induced radioresistance. A preexposure to ultraviolet light, or ionizing radiation followed by incubation to allow protein synthesis, followed by treatment with rifampin to prevent further induction, renders the cells resistant to further doses of radiation. When this is attempted with lambda lysogens of the same strains, no radioresistance is seen, even though the preexposure is too small to induce lambda itself. If the lysogens are ind-, namely lambda C1857, about the normal radioresistance can be developed by pretreatment. These findings suggest that the lambda repressors can bind to single-strand breaks caused by the inducing agent and can modify the course of induction. Abstract | PDF (377 kb) |
| Slug Antagonizes p53-Mediated Apoptosis of Hematopoietic Progenitors by Repressing puma Cell, Volume 123, Issue 4, 18 November 2005, Pages 641-653 Wen-Shu Wu, Stefan Heinrichs, Dong Xu, Sean P. Garrison, Gerard P. Zambetti, Jerry M. Adams and A. Thomas Look Summary In response to DNA damage, the p53 tumor suppressor can elicit either apoptosis or cell-cycle arrest and repair, but how this critical decision is made in specific cell types remains largely undefined. We investigated the mechanism by which the transcriptional repressor Slug specifically rescues hematopoietic progenitor cells from lethal doses of γ radiation. We show that Slug is transcriptionally induced by p53 upon irradiation and then protects the damaged cell from apoptosis by directly repressing p53-mediated transcription of , a key BH3-only antagonist of the antiapoptotic Bcl-2 proteins. We established the physiologic significance of Slug-mediated repression of by demonstrating that mice deficient in both genes survive doses of total-body irradiation that lethally deplete hematopoietic progenitor populations in mice lacking only . Thus, Slug functions downstream of p53 in developing blood cells as a critical switch that prevents their apoptosis by antagonizing the -activation of by p53. Summary | Full Text | PDF (709 kb) |
| Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity Cancer Cell, Volume 8, Issue 2, 1 August 2005, Pages 99-110 Benjamin J. Moeller, Matthew R. Dreher, Zahid N. Rabbani, Thies Schroeder, Yiting Cao, Chuan Y. Li and Mark W. Dewhirst Summary We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with “radiation first” strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics. Summary | Full Text | PDF (728 kb) |
Copyright © 1975 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 15, Issue 11, 1141-1154, 1 November 1975
doi:10.1016/S0006-3495(75)85890-5
Research Article
E.C. Pollard and P.M. Achey
The effect of prior treatment by inducing agents on the radioresistance of cells of Escherichia coli has been studied. In order to separate the induction process from the radiation-damage process, cells were first treated with inducing agents such as ultraviolet light, ionizing radiation, or nalidixic acid, allowed to become induced by incubation for 50min and then given rifampin to prevent further induction. They were then tested for radiation sensitivity. It was found that all strains tested except recA-, lex-, and recB showed very apparent protection. Induction by UV had the most effect and by nalidixic acid the least. The time course of development of protection was observed in one case: it is 50% established in 15min. The absence of effect in recA- and lex- is explainable by the fact that these cells cannot be induced, for example, for prophage or the inducible inhibitor of post-irradiation DNA degradation. We suggest that the inducible inhibitor of postirradiation DNA degradation is one factor in a recovery system possessed by E. coli cells.