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The effects of low doses of ionising radiation on the viability of mammalian cells

Marples, Brian; (1991) The effects of low doses of ionising radiation on the viability of mammalian cells. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The clonogenic response of V79-379A cells to single doses of X-rays (0.01-10 Gy) and neutrons (0.02-3 Gy) was determined using a computerised microscope (DMIPS) for locating and identifying cells. Survival estimates over the X-ray dose range 1 Gy to 10 Gy showed a good fit to a Linear-Quadratic (LQ) model. For X-ray doses below 0.6 Gy, an increased X-ray sensitivity was observed, with survival below the LX prediction. This phenomenon was not seen withneutrons, and cell survival decreased exponentially with dose. The increased X-ray effectiveness was reflected by a decrease in the RBE from -4.1 to 1.7 as the X-ray dose decreased from 1 Gy to below 0.05 Gy. Comparing the survival measurements from a DMIPS recognition assay with those obtained from a conventional assay suggest that this phenomenon cannot be attributed to the use of the recognition assay for measuring cell survival. Experiments performed on synchronised populations of cells indicate that the low-dose X-ray hypersensitivity is unlikely to be due to either cell cycle effects or a static subpopulation of X-ray sensitive cells. The X-ray dose response over the range 0.04-1 Gy was altered by repair modifiers in three ways. 3-aminobenzamide reduced the increase in radioresistance that occurred in non drug-treated cells as the X-ray dose was increased over the range 0.2-0.6 Gy, but did not affect the response below 0.2 Gy. Exposure to P-ara-A sensitised the cells to X-rays over the whole dose range (0.04-1 Gy) but did not prevent an increase in radioresistance with increasing X-ray dose. Hydrogen peroxide increased the radioresistance of cells to subsequent doses of X-rays below 0.6 Gy. The dose response was also modified by X-rays; a 0.05 Gy, 0.2 Gy or 1 Gy X-ray 'priming' treatment, given 4-6 hours before the 'test' doses of X-rays, eliminated the low-dose X-ray hypersensitivity that was seen in cells not given the priming treatment. This was not seen when the priming dose was administered 24 hours before the subsequent 'test' X-ray doses. These data are consistent with a hypothesis that the increase in radioresistance as the X-ray dose increases from 0.2-0.6 Gy is due to the manifestation of "induced repair" or a stress response: low doses (<0.2 Gy) are more effective, per gray, at killing cells than higher doses because only at higher doses (>0.2 Gy) is there sufficient damage to trigger the protective mechanism. An induced-repair model fitted to the X-ray data predicts that repair is activated in the dose range 0.2-0.6 Gy with a 2 fold decrease in the sensitivity between the very low-dose response (< 0.2 Gy) and the normal high-dose response (>0.6 Gy). Treatment with the protein synthesis inhibitor, cycloheximide, following a single dose of radiation reduced the increase in radioresistance that is seen normally over the X-ray dose range 0.2-0.6 Gy. Similarly, cycloheximide present during the interval between a priming dose and a subsequent X-ray dose eliminated the effect of the priming treatment. These data suggest that de novo protein synthesis is required to express the protective mechanism, possibly for the production of repair enzymes. A novel protein was detected in an irradiated sample of cells (1 Gy of X-rays) using 2D gel electrophoresis that was not present in unirradiated cells. These data appear to indicate that an inducible radioprotective mechanism exists in V79-379A cells that is triggered by H2O2 or small radiation doses and requires the synthesis of new proteins to induce radioresistance, possibly through a biochemical pathway affected by 3AB. The mechanism is induced within 4 hours of being triggered but is absent after 24 hours.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effects of low doses of ionising radiation on the viability of mammalian cells
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Pure sciences; Clonogenic response
URI: https://discovery.ucl.ac.uk/id/eprint/10122828
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