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High LET Radiation Overcomes in vitro Resistance to X-rays of Chondrosarcoma Cell Lines

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HAL Id: hal-03144579

https://hal.archives-ouvertes.fr/hal-03144579

Submitted on 25 Feb 2021

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High LET Radiation Overcomes in vitro Resistance to X-rays of Chondrosarcoma Cell Lines

Dounia Houria Hamdi, Charlotte Lepleux, Agnès Nicolle, Guillaume Varès, Paul Lesueur, François Chevalier

To cite this version:

Dounia Houria Hamdi, Charlotte Lepleux, Agnès Nicolle, Guillaume Varès, Paul Lesueur, et al.. High LET Radiation Overcomes in vitro Resistance to X-rays of Chondrosarcoma Cell Lines. ENLIGHT Annual Meeting and Training 2019, Jul 2019, Caen, France. �hal-03144579�

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DRF / iRCM – CIMAP Institut de Physique Université de Caen Normandie

LABORATOIRE D’EXCELLENCE INFRASTRUCTURE NATIONALE

EN BIOLOGIE ET SANTÉ

Centre de Recherche sur les Ions, les Matériaux et la Photonique

High LET Radiation Overcomes in vitro Resistance

to X-rays of Chondrosarcoma Cell Lines

Hamdi D.H.

1,2

, Lepleux C.

1,2

, Nicol A.

3

, Varès G.

4

, Lesueur P.

5

and Chevalier F.

1,2

1 LARIA – Cimap / iRCM - Commissariat à l’Energie Atomique et aux Energies Alternatives, Caen, France ; 2 Normandie Univ, ENSICAEN, UNICAEN, CEA, CNRS, CIMAP UMR6252, 14000 Caen, France;

3 Radiobiology Laboratory, IPHC UMR 7178, Centre Paul Strauss, UNICANCER, Université de Strasbourg, Strasbourg, France; 4 Cell Signal Unit, OIST, Onna-son, Okinawa, Japan;

5 Centre Francois Baclesse, Radiotherapy Unit, Caen, France

Chondrosarcoma is a malignant tumor arising from cartilaginous tissues, described as radiation- and chemo- resistant to conventional treatments. The primary treatment consists in wide surgical resection, which may lead to severe disabilities; in addition, this procedure is not feasible for

some inoperable locations such as skull base

chondrosarcoma. Carbon-ion irradiation (hadron-therapy) has been successfully used in the treatment of chondrosarcoma, due notably to a higher biological effectiveness and a better ballistic as compared with conventional radiotherapy with X-Rays.

The aim of this study was to examine the differential cellular responses of chondrosarcomas to conventional radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Four human chondrosarcoma cell lines of different grades and displaying differential radio-sensitivities, were irradiated with photons (250 kV, 2Gy/min) or carbon ions (95 MeV/A, LET 33 keV/µm).

REF : from Chevalier et al., TCRT, 2019, in press

Aim of this study

- explore the differential cellular responses of

chondrosarcomas to conventional radiotherapy and hadrontherapy

- understand the biological effects of carbon beams in cancer treatment

Irradiations / treatments

Four human chondrosarcoma cell lines of different grades were used : SW1353 GII, L835 G II, CH2879 GIII and OUMS27 GIII

Cells were irradiated with X-Rays (X-Rad 225 Cx), or with

Carbon ions of two LET and analyzed by :

- clonogenic assays

- Micro-nuclei assays

- Cell cycle analyses

- Western blotting (P21 / g-H2AX)

ENLIGHT Annual Meeting and

Training 2019, Caen

D10a D37b SF2c RBE (D10)d RBE (D37)e SW1353 X-Rays* 1.3 keV/µm 6.84 +/- 0.51 3.74 +/- 0.64 0.64 +/- 0.09 / / Carbon** 28 keV/µm 2.94 +/- 0.19 1.27 +/- 0.08 0.21 +/- 0.02 2.32 2.95 Carbon** 73 keV/µm 1.34 +/- 0.02 0.58 +/- 0.01 0.03 +/- 0.00 5.11 6.51 CH2879 X-Rays 1.3 keV/µm 5.92 +/- 0.29 3.43 +/- 0.16 0.63 +/- 0.05 / / Carbon 28 keV/µm 2.47 +/- 0.28 1.07 +/- 0.12 0.15 +/- 0.03 2.40 3.22 Carbon 73 keV/µm 1.08 +/- 0.01 0.47 +/- 0.01 0.01 +/- 0.00 5.48 7.37 OUMS27 X-Rays 1.3 keV/µm 6.76 +/- 0.50 3.44 +/- 0.18 0.57 +/- 0.03 / / Carbon 28 keV/µm 3.29 +/- 0.25 1.42 +/- 0.11 0.24 +/- 0.03 2.05 2.42 Carbon 73 keV/µm 1.30 +/- 0.10 0.56 +/- 0.05 0.03 +/- 0.01 5.18 6.15 L835 X-Rays 1.3 keV/µm 4.16 +/- 0.11 1.93 +/- 0.16 0.36 +/- 0.03 / / Carbon 28 keV/µm 1.65 +/- 0.05 0.71 +/- 0.02 0.06 +/- 0.01 2.52 2.70 Carbon 73 keV/µm 1.12 +/- 0.01 0.48 +/- 0.01 0.02 +/- 0.00 3.72 3.99

Western Blotting : SW1353

Clonogenic assays: all cells

Cell cycle analysis : SW1353

Micro-nuclei assays : SW1353

Chondrosarcoma cells showed a heterogeneous sensitivity towards irradiation s:

- Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using

D10 values, the relative biological

effectiveness of C-ions was higher (RBE = 5.5) with cells resistant to X-rays (CH2879) and lower (RBE = 3.7) with sensitive cells (L835). - C-ions induced more G2 phase blockage and

micronuclei in SW1353 cells as compared to X-rays with the same doses.

- Persistent un-repaired DNA damage was also higher following C-ions irradiation.

These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however treatment with C-ions irradiation was more

efficient in killing chondrosarcoma cells,

compared with X-rays.

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