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Madas Balázs

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Madas Balázs
Metastatic potential of HeLa-cells does not increase directly after radiation exposure

Aug 29 - kedd

14:20 – 14:40

Orvosi biofizika és sugárbiológia

E15

Metastatic potential of HeLa-cells does not increase directly after radiation exposure

Balázs Madas¹, Kinga Kovács², Andrea Strádi³, Szabolcs Polgár⁴, Inna Székács⁵, and Róbert Horváth⁵

¹ Centre for Energy Research, Environmental Physics Department, Budapest, Hungary

² Centre for Energy Research, Nanobiosensorics Department, Budapest, Hungary

³ Centre for Energy Research, Space Research Department, Budapest, Hungary

While radiation therapy increases local tumor control, it remains controversial whether ionizing radiation increases the metastatic potential of cancer cells. One of the potential mechanisms of radiation-induced metastasis is the direct release of tumor cells into the circulation requiring the detachment of the cells. The objective of the present study was to directly measure how ionizing radiation affects the kinetics of cellular adhesion, especially its initial stage after cell attachment on a biomimetic surface.

For this purpose, an automatic irradiation facility with gamma-radiation from Cs-137 has been developed providing parallel irradiation opportunity of 96 wells of a biosensor microplate with different doses. The employed optical biosensor records the wavelength shift of reflected light from a nanostructured waveguide, being proportional to the cell adhesion strength. Absorbed doses were measured by thermoluminescent dosimeters (TLDs) in each well. As a model system, a cervical cancer cell line (HeLa) was studied.

Three different experimental setups have been used distinguished by the sequence of irradiation and cellular attachment to the surface. The wavelength shift as the function of time was measured for different absorbed doses. The maximum wavelength shift as the function of dose was also analyzed.

The results show that adhesion of HeLa cells is not affected by ionizing radiation in the first hours after irradiation. The result is independent of whether cells are exposed during the adhesion process, in suspension, or attached. This suggests that radiation therapy does not directly increase the metastatic potential of cancer cells by decreasing their adhesion.

The experimental setup can be used to quantify the effects of ionizing radiation on cell adhesion as the function of time at different absorbed doses. It has been shown that ionizing radiation does not affect the adhesion of HeLa cells in the first hours after exposure, while experiments with longer follow-up are required to see whether adhesion changes at later time points.

Polgár Szabolcs
Mathematical modelling of low dose hyper-radiosensitivity and induced radioresistance

Aug 29 - kedd

15:30 – 17:00

I. Poszterszekció

P22

Mathematical modelling of low dose hyper-radiosensitivity and induced radioresistance

Szabolcs Polgár^1,2, Balázs Madas^2,3

¹ Doctoral School of Physics, ELTE Eötvös Loránd University, Budapest, Hungary

² Environmental Physics Department, Centre for Energy Research, Budapest, Hungary

³ Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Budapest, Hungary

The surviving fraction of cells decreases exponentially with the increase of the absorbed dose at high doses. At low doses however, experiments show that in many different cell lines the surviving fraction differs from this, due to the effects of hyper-radiosensitivity and induced radioresistance [1]. The result is a function that starts steeper and after a local minimum starts to increase to a local maximum as the dose increases before following the exponential decrease at higher doses.

The aim of this study was to test if the principle of minimum mutation load [see e.g., 2] can describe both hyper-radiosensitivity and induced radioresistance at low doses. In this case the principle means that the most damaged cells in a vicinity use apoptosis to reduce the mutation rate in the tissue.

To test this hypothesis a mathematical model was developed and an experimental database constructed from published articles for validation.

For the model validation a database was used, consisting of various experimental data featuring low dose hyper-radiosensitivity [3]. The model has been developed in Python. A total of 600 cells are placed randomly in a circle with a given radius. The cells are able to communicate their DNA damage by a signal, its concentration following normal distribution, centered on the cell. The DNA damage of the cells follow Poisson distribution for any given dose.

The fit parameters for the model were acquired by fitting with the Nelder-Mead method to the experimental data in each case. The parameter calculation consisted first a preliminary calculation (using the starting slope and the local minimum of each dataset) to acquire the initial parameters, then a two dimension fit with the Nelder-Mead method was calculated to reach the best values for them. The results then were evaluated and compared to the induced repair model where possible (where there was a fit in the original article).

Acknowledgment

This study is part of the RadoNorm project which has received funding from the Euratom research and training programme 2019-2020 under grant agreement No. 900009. The study was also supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (bo-37-2021) and the ÚNKP-22-5 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (ÚNKP-22-5-BME-299).

References

[1] Marples, B., Collis, S.J., 2008. Low-Dose Hyper-Radiosensitivity: Past, Present, and Future. International Journal of Radiation Oncology*Biology*Physics 70, 1310–1318. https://doi.org/10.1016/j.ijrobp.2007.11.071

[2] Derényi, I., Szöllősi, G.J., 2017. Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations. Nature Communications 8, 14545. https://doi.org/10.1038/ncomms14545

[3] Polgár, S., Schofield, P.N., Madas, B.G., 2022. Datasets of in vitro clonogenic assays showing low dose hyper-radiosensitivity and induced radioresistance. Sci Data 9, 555.

https://doi.org/10.1038/s41597-022-01653-3