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Adaptive response induced by different dose rates of γ-radiation in MCF-10A cells
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses are of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (24 Gy/h) or chronically (1.4 or 4.1 mGy/h). After 2 hours incubation time cells were exposed to a challenging dose of 1 to 5 Gy. Adaptive response was absent at the level of clonogenic survival and present at the level of mutations only at 1.4 mGy/h administration of adapting dose. Overall, no dose rate effect of the adapting dose was observed at the level of clonogenic survival, while it was seen at the frequency of mutants. On the other hand, a dose rate effect was absent at the level of mutant frequency.

Keyword [en]
Adaptive response, low dose rate, ionizing radiation, mutation rate
National Category
Biological Sciences
Research subject
Molecular Genetics
Identifiers
URN: urn:nbn:se:su:diva-114310OAI: oai:DiVA.org:su-114310DiVA: diva2:791137
Available from: 2015-02-26 Created: 2015-02-26 Last updated: 2016-01-29Bibliographically approved
In thesis
1. Role of MTH1 and MYH proteins in genotoxic effects of radiation
Open this publication in new window or tab >>Role of MTH1 and MYH proteins in genotoxic effects of radiation
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Humans are constantly exposed to different types of radiations. It has been suggested that low dose and low dose rate of γ-radiation as well as ultra violet A (UVA) induce oxidative stress in cells that may promote mutations. The mechanisms behind radiation-induced oxidative stress and its relation to genotoxicity and cancer induction are not well understood. In the majority of investigations, the DNA molecule has been studied as the target for mutations, however the results obtained in our group point out that DNA bases in the cytoplasm could also be a significant target. MTH1 and MYH are two of the key proteins of the repair pathway that prevent mutations arising from oxidized DNA bases. In this thesis, we studied the role of MTH1 and MYH in genotoxicity of UVA and γ-radiation. The adaptive response to low dose rates of γ-radiation was also investigated. MTH1 and/or MYH were knockdown in human lymphoblastoid TK6 cells. The clonogenic survival, mutant frequency and chromosomal aberration assays were performed following UVA or γ-radiation exposure. Our results indicated that acute exposure to UVA or γ-radiation affects cell survival and also increases the mutant frequency above the background. The mutant frequency in MTH1 deficient cells was higher than that in wild types after UVA exposure. Following γ-radiation exposure, a higher mutant frequency was observed in the MYH and MTH1 deficient cells, in comparison to either MYH or MTH1 deficient or wild type cells. No dose rate effect of γ-radiation for mutations was observed. An adaptive response to γ-radiation was observed at the mutation level in MCF-10A cells but not at the survival level. In summary, our results suggest that; a) MYH and MTH1 cooperatively protect cells against genotoxic effects of γ-radiation; b) MTH1 protects cells from UVA-induced mutations; c) low dose rates of γ-radiation may induce an adaptive response at the mutation level; d) there is no dose rate effect for γ-radiation at the mutation level.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2015. 45 p.
Keyword
MTH1, MYH, gamma radiation, UV radiation, oxidative stress, low dose rate ionizing radiation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-113835 (URN)978-91-7649-099-0 (ISBN)
Public defence
2015-03-30, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.

Available from: 2015-03-09 Created: 2015-02-12 Last updated: 2015-03-18Bibliographically approved

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