Combination of agents modifying effects in hadrontherapy: modelization of the role of HO° free radicals

Abstract

Purpose: A study is presented of the irradiation of cancerous cervical cell line HeLa loaded with a platinum salt, betamethasone and deoxyglucose. The presence of the platinum increases the free-radical concentration and augments the cell death rate, whereas betamethasone or deoxyglucose induces radiosensitization by the alteration of metabolic pathways. Two by two combinations of these chemicals are made to investigate the possible benefit when two radiosensitizers are present. A model is proposed to understand the results of the presence of two modifying agents on the dose effects.

Materials and methods: The cells were incubated for 6 h in the presence of the following molecules: dichloro terpyridine platinum, concentration C = 350 μM, betamethasone and deoxyglucose with concentrations of C = 0.2 μM and C = 6 mM, respectively. The cells were subsequently irradiated by carbon C⁶⁺ ion 290 MeV/amu up to a dose of 2.5 Gy, under atmospheric conditions.

Results: The presence of the platinum salt or bethamethasone augments the cell death rate. The combination of betamethasone with the platinum salt also increases the cell death rate, but less than for the platinum salt alone. The explanation is that any radiosensitizer also behaves as a scavenger of free radicals. This dual behavior should be considered in any optimization of the design of radiosensitizers when different ionizing particles are used.

Keywords:

• Radiosensitizers
• platinum salt
• glucocorticoid
• deoxyglucose
• hadrontherapy
• cervical cancer cell

Acknowledgments

This work was supported by the Research Project with Heavy ions at NIRS-HIMAC (Project number J331). The authors are indebted to Dr Andrew Mayne for careful reading of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

Noriko Usami

Noriko Usami, PhD in biology at Tsukuba University (1992). Associate Professor at Photon Factory (PF), Institute of Materials Structure Science (IMSS), High Energy Accelerator Research Organization (KEK), Japan. She is a beamline scientist of PF and interested in mechanisms for biological radiation responses.

Ryoichi Hirayama

Ryoichi Hirayama, PhD, is a Senior Researcher at Department of Charged Particle Therapy Research, NIRS, QST. His research field is radiation biophysics, and his interest is the track structure of heavy ion and its effect in hypoxia.

Katsumi Kobayashi

Katsumi Kobayashi, PhD in Biophysics at the Tokyo University (1977). Professor, Head of Research Service Office, High Energy Accelerator Research Organization (KEK), Japan. The domains of research are the damages analysis in biomolecules, and living cells, induced by monochromatic X-rays, including the study of the bystander effect.

Yoshiya Furusawa

Yoshiya Furusawa, PhD, is a Researcher at NIRS, QST. His research field is radiation biology, and his interest is the biological effect of heavy-ions.

Claude Le Sech

Claude Le Sech, PhD, MD, Professor of Physical Chemistry at Paris-Saclay University. He begun to study the damages of DNA loaded with high-Z atoms, induced by monochromatic photons. These studies lead him to extend in hadrontherapy this approach to cancerous cells added with high-Z atoms, or metabolic radiosensitizers.