UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

Guest
2024-11-23 18:27
 HOME     CONFERENCES     SEARCH            LOGIN     NEW USER     IMAGES   


Conference: Bucharest University Faculty of Physics 2016 Meeting


Section: Biophysics; Medical Physics


Title:
Cellular Differentiation Exacerbates Radiation Sensitivity in Vitro in a Human Dopaminergic Neuronal Model


Authors:
Mihaela TEMELIE (1), Cosmin MUSTACIOSU (1), Diana SAVU (1)


Affiliation:
1) Department of Life and Environmental Physics, National Institute of Physics and Nuclear Engineering Horia Hulubei


E-mail
mihaela.temelie@nipne.ro


Keywords:
UV, radiation, cells, differentiation, DNA repair


Abstract:
Ultraviolet (UV) radiation is a well known cellular stressor, able to induce various molecular lesions, one of the most harmful of them being the DNA damage. Following exposure to genotoxic factors the cells respond by activating a complex of molecular mechanisms in order to repair the lesions or, in case of extensive damage, to block the proliferation and trigger cell death. Our study aimed to investigate the relevance of the differentiation stage in a model of human dopaminergic neurons (SH-SY5Y) in modulating the response to UV induced cellular damage by comparing dividing/non-differentiated cells with non-dividing/differentiated cells. Cells were differentiated in vitro following a standard protocol based on addition of retinoic acid to the culture medium. At 7 days of differentiation the cultures were irradiated with a UV lamp at 254 nm, using doses of 1.5-5.20 mJ/cm2 in parallel with undifferentiated control cells. Following irradiation we evaluated the induction and repair of DNA damage, the evolution of cellular viability and apoptosis level up to 24 hours post-irradiation. Our work proved a higher level of DNA damage induced by UV in differentiated cells compared to proliferative variant. The DNA damages are repaired in time. Cellular viability decreased proportional with the irradiation dose and time of incubation post-exposure in both models, but the effect is enhanced in differentiated SH-SY5Y cells. Investigation of mechanism of cellular death proved that caspase 3/7 activation, which occurs from 6 hours post-irradiation, is involved in triggering apoptosis. This process is also intensified in differentiated cells. In conclusion, our findings showed that cellular differentiation increases UV sensitivity in SH-SY5Y dopaminergic neurons, impairing DNA repair and enhancing cellular death by apoptosis.


References:

P. Fortini, E. Dogliotti (2010): Mechanisms of dealing with DNA damage in terminally differentiated cells, Mut. Res., 685(1–2):38–44. doi:10.1016/j.mrfmmm.2009.11.003

T. Nouspikel (2007): DNA repair in differentiated cells: Some new answers to old questions, Neurosci., 145(4): 1213–1221. doi:10.1016/j.neuroscience.2006.07.006

Melissa LF, Michael RV, Mark RK (2007): DNA repair in neurons: So if they don’t divide what's to repair? Mut Res, 614 (1–2) 24–36 doi:10.1016/j.mrfmmm.2006.06.007

Acknowledgement:
The work was supported by Romanian Ministry of Research by National grants Nos. PN 09370301, PN-II-ID-PCCE-2011-2-0027 and PN-II-123/2012.