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

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