The Repair Time of Chromosome Breaks Induced by Pulsed X-rays of Ultra-high Dose-rate

Abstract

IntroductionIt was first cited by Sax (1939) that at a given dose of x-ray the frequency of two-hit-type chromosome aberrations decreased with decreasing dose rates. This led Sax (1939Sax ( , 1940 to carry out fractionation experiments which indicated that the exchange process was the result of interaction of induced breaks that were time and space dependent. Subsequently, Wolff demonstrated that chromosome breakage and repair were separable but related events (Wolff and Atwood 1954). Wolff again showed that exchange formation between breaks (lesions) induced by two fractions of x-ray was dependent on their being present at the same time. That is, no repair of breaks (lesions) created by the first fraction had taken place before the production of subsequent breaks (lesions). Changes in dose-rate at a given dose did not appear to alter the amount of primary breakage but rather limited the opportunity for repair. The experiment performed by Brewen (1963), using Chinese hamster corneal epithelium, indicated that at a total dose of 50 or 100 R, the observed chromosomal breaks were highest when dose-rate was 600 R/min and significantly lower when it was 2 R/min. However, when cells were pre-treated with puromycin (an inhibitor of protein synthesis), the total breaks induced by each dose-rate, 2 R/min, and 600 R/min, were the same (Brewen 1963). It seemed then that the primary chromosomal breaks (lesions) at the doses studied were the same regardless of the dose-rate used but that subsequent repair of the breaks (lesions) seemed to be responsible for the variation in the number of observed aberrations. Repair then seems to be a more successful process when x-ray treatments are given at a very low dose-rate and vice versa. It should follow then that ultra-high dose-rate might result in increases in the frequency of chromosomal aberrations. On the contrary, Kirby-Smith and Dolphin (1958) found that two-hit aberrations were only 40-50 per cent of the frequency seen at a dose-rate of 1 x 106 rads/sec when the rate was increased to 4 x 108 rads/sec and the treatments given in air. Moreover the difference in two-hit yields produced by the different dose-rates did not exist when the studies were performed in an atmosphere of nitrogen. The difference in the observed results was, therefore, ascribed to temporary and partial anoxia induced by the high dose-rate (Thoday and Read 1947) rather than the possible recombination of secondary organic free radicals. Michelsen in his recent study comparing the effect of the dose-rate between 2.7 x 1012 R/min (4.5 x 1010 R/sec) and 100 R/min, has also observed results that showed that

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“…For mammalian cellular and chromosomal systems, interesting results were published by several authors between 1967 and 1978. These led to the conclusion that ultra-high dose rates would not necessarily be advantageous and might have adverse consequences because of local oxygen depletion [2][3][4][5][6][7][8][9], with very low oxygen tensions causing significant cellular radioresistance and being capable of reducing local cancer ''cure''.…”

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