A Model Relating Cell Survival to DNA Fragment Loss and Unrepaired Double-Strand Breaks

Abstract

The model of radiation action that is presented relates the surviving fraction of irradiated cells to unrepaired DNA double-strand breaks (DSBs). The following assumptions are made in the model: (i) A DNA fragment created by the induced DSBs may move out of its chromosome (become lost), and the probability of that process depends on the fragment size. (ii) An irradiated cell will lose its proliferative capacity if it has an unrepaired DSB (including DNA fragments) at certain points in the cell cycle. Mathematical expressions of the model yield the dose and time dependencies of the surviving fraction, the number of unrepaired DSBs, and the number of prematurely condensed chromosome fragments. Radiobiological phenomena described include effects of low dose rate, delayed plating, hypertonic solution, araA, and high-LET radiation. The calculated dose dependence of the residual number of unrepaired DSBs for ataxia telangiectasia and normal fibroblast cells is very close to the experimentally obtained [M. N. Cornforth and J. S. Bedford, Radiat. Res. 111, 385-405 (1987)] total number of chromosomal aberrations. This leads to the conclusion that each unrepaired DSB becomes a chromosomal aberration. Analysis in terms of the model shows that the radiosensitivity of various cell lines is predominantly due to the different amounts of time available for DSB repair in these cells.

The effect ofin vivoresveratrol supplementation in irradiated mice on the induction of micronuclei in peripheral blood and bone marrow reticulocytes

“…Then RSV is not protector against cell killing in vitro or lethality in vivo (54). However, results of other studies may indicate that it would protect against lethality, but the doses of irradiation used were much lower (55,56). Above results were confirmed by our, where the mortality of mice from groups of 1 Gy + RSV were higher compared to 1 Gy alone, and clear mitigation of DNA damage was seen after combined exposure to 0.5 Gy daily and RSV.…”

Prediction of Cell Survival Curves from DNA Double-strand Break Repair Data for Low- and High-LET Radiation

“…On the other hand, the residual unrepaired dsb represent dsb remaining in a DNA molecule until the moment when the time available for dsb repair (t fep) is over . It was shown that the residual unrepaired dsb become new DNA fragments or 'misrepair' chromosomal aberrations (CA) after t rep has elapsed .Several quantitive estimates from the model, which agree with experimental data, support the validity of this model (Ostashevsky 1989) : (1) the number of PCC fragments and the total number of CA for AT, normal fibroblasts (NF) and LY-R cells ;(2) an increase in the number of 'misrepair' CA for NF cells treated with araA ;(3) tfep values for AT, NF and Ehrlich ascites tumour (EAT) cells (see § 2 .2 .3 for EAT cells) ; (4) the difference between t ree values for delayed and immediately plated NF and V-79 cells . More details of the model are given in § 2 .…”

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A model developed previously (Ostashevsky 1989), was applied to calculate survival curves from the DNA double-strand break (dsb) repair data for Ehrlich ascites tumour (EAT) cells irradiated with X-rays or 3 . 4 MeV a-particles (Blucher 1988) .

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Damage at two levels of DNA folding measured by fluorescent halo technique in X-irradiated L5178Y-R and L5178Y-S cells. II. Repair

“…30% ALSs, 63-67% SSBs, and 4-7% DSBs) are the lesions most responsible for opening the condensed chromatin structure after irradiation, seen as EHD. The decondensation of chromatin may be prerequisite for the loss of DNA fragments (between two DSBs), an event postulated to occur very early post irradiation in the DSB model (Ostashevsky 1989(Ostashevsky , 1990. Thus, although the repair rates measured here for EHD are consistent with SSB repair, they could be very important for determining the fraction of DSBs repaired and survival.…”