The Relationship between Radiation-induced DNA Double-strand Breaks and Cell Kill in Hamster V79 Fibroblasts Irradiated with 250 kVp X-rays, 2·3 MeV Neutrons or²³⁸Pu α-particles

Abstract

Using the neutral filter elution technique, the induction of DNA double-strand breaks (dsb) has been measured in 250 kVp X-irradiated V79-379A Chinese hamster cells irradiated under air or nitrogen. The dose-effect curves for induced dsb were curvilinear, mirroring cell survival curves, such that there was an approximately linear relationship between induced dsb and lethal lesions (-In (cell survival)) which was independent of oxygen. With cells irradiated with 2.3 MeV neutrons or 238Pu alpha-particles the correlations between lethal events and dsb, although also approximately linear, do not match those for X-rays. With neutrons there is approximately a 2.5-fold reduction in the level of dsb induction per lethal event. Thus either the apparently linear relationships found are spurious, and there is no general correlation between induced dsb and lethal effect, or there are qualitative differences between neutron, alpha-particle and X-ray induced dsb that give them differing probabilities of cell kill.

Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells

“…The RBE of 1 derived for the induction of DNA-DSBs is consistent with published results obtained with other methods at higher doses as summarised by Prise et al (46). However, Prise et al (46) observed a significant contribution of the quadratic parameter β for DNA-DSBs measured by the filter elution technique in the dose-effect curves at large doses of X-rays (46,47) and a linear-quadratic relationship for X-rays was demonstrated.…”

“…Though there is a clear correlation between cell reproductive death and the induction of chromosomal aberrations assessed by PCC, a direct causal relationship between these effects cannot yet be inferred, because the repair occurring after irradiation might act differently for the two radiation types (46). Further studies of RBE values for cells at different time intervals post irradiation will yield information on this problem.…”

SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours

“…Such high local concentrations of radicals could produce highly damaged DNA similar to that produced by densely ionising radiation. Breaks such as these are less repairable than those produced by sparsely ionising radiation such as X-rays (Bedford & Goodhead, 1989;Prise et al, 1987). …”

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

“…Its relationship to clonogenic cell survival has been studied by several investigators and correlations were found in some studies (Radford, 1986;Prise et al, 1987) though not all (McMillan et al, 1990). A weakness of this approach has been that the dose range of the end points does not overlap; to generate a measurable number of double-strand breaks, much higher radiation doses are required than are appropriate for the clonogenic assay or in the clinical setting.…”