Scaling parameter of the lethal effect of mammalian cells based on radiation-induced OH radicals: effectiveness of direct action in radiation therapy

Abstract

We have been studying the effectiveness of direct action, which induces clustered DNA damage leading to cell killing, relative to indirect action. Here a new criterion Direct Ation-Based Biological Effectiveness (DABBLE) is proposed to understand the contribution of direct action for cell killing induced by C ions. DABBLE is defined as the ratio of direct action to indirect action. To derive this ratio, we describe survival curves of mammalian cells as a function of the number of OH radicals produced 1 ps and 100 ns after irradiation, instead of the absorbed dose. By comparing values on the vertical axis of the survival curves at a certain number of OH radicals produced, we successfully discriminate the contribution of direct action induced by C ions from that of indirect action. DABBLE increases monotonically with increasing linear energy transfer (LET) up to 140 keV/μm and then drops, when the survival curves are described by the number of OH radicals 1 ps after irradiation. The trend of DABBLE is in agreement with that of relative biological effectiveness (RBE) of indirect action. In comparison, the value of DABBLE increases monotonically with LET, when the survival curves are described by the number of OH radicals 100 ns after irradiation. This finding implies that the effectiveness of C ion therapy for cancer depends on the contribution of direct action and we can follow the contribution of direct action over time in the chemical phase.

DNA strand break induction of aqueous plasmid DNA exposed to 30 MeV protons at ultra-high dose rate

“…If the case, the FLASH effect would be strongly dependent on the radiation quality that results radiological process of indirect action and high oxygen enhancement ratio. The proton beam in this study was a 27.5 MeV proton which has G(OH)100 eV of ~3 and OER that are equivalent to that of X-rays and gamma-rays [ 22 , 30 , 38 , 39 ].…”

“…Indeed, the FLASH effect would strongly correlate on radiation types. For example, charged particles near the Bragg peak are well known to have high LET with highly localized dose distribution along its tracks [ 37 ] that result in a small oxygen enhancement ratio [ 38 , 39 ]. It is explained as a result of small G(OH) value [24, 32] and low consumption of the molecular oxygen per 100 eV at charged particles with high LET that drastically decrease near the Bragg peak [ 12 ].…”

Estimation of biological effect of Cu-64 radiopharmaceuticals with Geant4-DNA simulation

“…Previously, we implied that the number of OH radicals produced could become a universal parameter for expressing the biological effect 43 . Thus, based on the number of OH radicals produced, we could universally express the biological effect under ionizing radiations with different radiation qualities 30 .…”

The ‘stealth-bomber’ paradigm for deciphering the tumour response to carbon-ion irradiation

“…Moreover, the composition of the LMDS and the following repair pathways involved could depend on the cell type but also on the dose and the LET, which adds another level of complexity to their repair [20]. A recent study investigated the contribution of the direct effects of C-ions compared with their indirect action through the prism of OH • formation in relation to the cell killing resulting from clustered damage [21]. They concluded that the efficacy of C-ions in cell death results from the contribution of OH • produced in the track, which is in favour of the 'bomber' effect.…”