Contributions of Direct and Indirect Actions in Cell Killing by High-LET Radiations

Abstract

The biological effects of radiation originate principally in damages to DNA. DNA damages by X rays as well as heavy ions are induced by a combination of direct and indirect actions. The contribution of indirect action in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action without affecting direct action. Exponentially growing Chinese hamster V79 cells were exposed to high-LET radiations of 20 to 2106 keV/mum in the presence or absence of DMSO and their survival was determined using a colony formation assay. The contribution of indirect action to cell killing decreased with increasing LET. However, the contribution did not reach zero even at very high LETs and was estimated to be 32% at an LET of 2106 keV/mum. Therefore, even though the radiochemically estimated G value of OH radicals was nearly zero at an LET of 1000 keV/mum, indirect action by OH radicals contributed to a substantial fraction of the biological effects of high-LET radiations. The RBE determined at a survival level of 10% increased with LET, reaching a maximum value of 2.88 at 200 keV/mum, and decreased thereafter. When the RBE was estimated separately for direct action (RBE(D)) and indirect action (RBE(I)); both exhibited an LET dependence similar to that of the RBE, peaking at 200 keV/mum. However, the peak value was much higher for RBE(D) (5.99) than RBE(I) (1.89). Thus direct action contributes more to the high RBE of high-LET radiations than indirect action does.

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

“…McMahon et al, 2011a andLeung et al, 2011, simulated secondary electron emission from individual GNPs and postulated that local dose enhancement from short range Auger electrons mimicked the enhanced relative biological effect of heavy ions. With heavy ions, a comparable dose can be deposited to an equivalent dose of X-rays but the survival fraction of cells is much lower (Hirayama et al, 2009). The dose is localised to the ion-track and results in many more lethal double-strand breaks than the same dose spread homogenously.…”

“…(Bishayee et al, 2000) showed that DMSO protected cells from 125 I-and 131 I-iododeoxyuridine ( 125 IdU, 131 IdU) β-emitters, but not against 210 Po emitting 5.3 MeV α particles. Various experimenters have shown that DMSO can protect about 75% of the damage from X-rays (Hirayama et al, 2009, Shinohara et al, 1996. Interestingly, the degree of protection that DMSO affords high-LET radiation, depends on the energy (or LET) of the particle, with those near the Bragg peak imparting much more direct-action damage as one would expect.…”

“…This is most likely due to the energy of the ions interacting with nanoparticles. With proton beam energies above 40 MeV, the LET of the ions as it traverses the cells is below 5 keV µm -1 , while with 3 MeV protons it is above 10 keV µm -1 (Hirayama et al, 2009). …”

“…Charged particles are much more densely ionising than X-rays, and the contribution of direct action to cell killing is much greater. For example, with 16 MeV iron particles about 70 % of the cell death is caused by direct action (Hirayama et al, 2009) Immediately prior to the irradiation with both X-rays and protons, the cells were incubated with media containing 1M of DMSO. This is non-toxic for short durations (Hirayama et al, 2009).…”

Review of Geant4-DNA applications for micro and nanoscale simulations

“…They will be required for the simulation of indirect effects of ionising radiation to DNA. Such effects are known to be dominant especially in the low LET domain (see for example Hirayama et al [43]). …”