Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
QUALITATIVE DISTINCTIONS OF DOSE-EFFECT RELATIONSHIPS BETWEEN DIFFERENT STRESS RESPONSES TO IONIZING RADIATION IN NORMAL HUMAN FIBROBLASTS I.O. Velegzhaninov1, A.V. Ermakova1, D.M. Shadrin1, Y.I. Pylina1, O.A. Shostal1, E.S. Belykh1, A.V. Kaneva1, O.V. Ermakova1, D.Y. Klokov2 1 Institute of Biology, Komi Science Center of RAS, Syktyvkar, Russia. 2 Canadian Nuclear Laboratories, Chalk River, Ontario, Canada Understanding the mechanisms producing low dose ionizing radiation specific biological effects represents one of the major challenges of radiation biology. Although experimental evidence does suggest that various molecular stress response pathways may be involved in the production of low dose effects, much of the detail of those mechanisms remains elusive. We hypothesized that the regulation of various stress response pathways upon irradiation may differ from one another in complex doseresponse manners, causing the specific and subtle low dose radiation effects. To verify this hypothesis in the present study, the DNA damage induction, DNA repair, caspase-3 induction, and the transcription level of 22 genes involved in stress responses were analyzed in normal human fibroblasts (HELF-104) exposed to a range of gamma-doses from 1 to 200 cGy. Furthermore, the senescence dynamic of irradiated cell were analyzed using histochemical staining for β-galactosidase until a complete stop of culture growth. We found non-linear dose responses for the repair of DNA damage after exposure to gamma-radiation. Alterations in gene expression were also not linear with dose for several of the genes examined and did not follow a single pattern. Rather, several patterns could be seen. In addition, qualitatively different changes in dynamic of βgalactosidase accumulation in cells irradiated by different doses were shown. Low dose irradiation may delay the onset of senescence in normal human fibroblasts. The latter result confirms our earlier data, that shows for the first time the effect of radioinduced delay of senescense in HFL-1 cell line. Our results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for reactions of different systems. Funding for this study was provided by the Russian Fund for Fundamental Research Grant 13-04-01750.