On the formation kinetics of radiation-induced chromosome exchanges in human lymphocytes

Abstract

In their recent paper on modelling the kinetics of chromosome exchange formation [1], Moiseenko et al. comment upon the observation of Vyas et al. [2] made at doses of 2 and 3 Gy that the yield of radiation-induced dicentric chromosomes in human interphase lymphocytes seen under conditions of premature chromosome condensation (PCC) at fusion delay times up to 2 h was similar to the yield observed in the first metaphase after stimulation with phytohemagglutinin (PHA). Moiseenko et al. think that this lack of a detectable difference was the reason why Vyas et al. did not increase the delay time further. However, in our subsequent study [3] at a dose of 4 Gy, a significant additional yield contribution solely ascribable to the βD 2 component was observed at longer delay times up to 14 h [3]. This contrast is interesting, especially with regard to the design of further experiments, because of the great influence of the chosen dose level upon the detectability of the delayed yield increase.In order to illustrate this, we have plotted in Fig. 1 the dose-dependent yield of dicentrics seen under PCC conditions for fusion delay times t D of 0 and 8 h (taken from [3]) and the yields observed in the first metaphase after PHA stimulation (taken from [4] and new unpublished data, R. P. Virsik-Peuckert). It is true that at D = 2 Gy and even at D = 3 Gy, statistical limits of uncertainty may prevent the detection of any yield difference between the observation at t D = 0 h and the two other conditions. However, at D = 4 Gy, where we studied the change of the dicentric yield with fusion delay time [3], the yield difference cannot be masked by measurement uncertainty, and it would be even more prominent in an experiment performed at 5 Gy. We conclude that the yield of radiation-induced dicentrics seen under PCC conditions at long fusion delay times closely resembles the yield seen in first metaphase, while the yield for short delay times is significantly smaller at doses exceeding 3 Gy.It is worth noting that the linear term at t D = 8 h is only about two-thirds of that seen at t D = 0 h [3], a reduction of opposite tendency to the increase of the dose-squared term with increasing delay time. This partial compensation contributes to the difficulties in detecting any yield differences at smaller doses. From a mechanistic point of view, this reduction of the linear term with increasing delay time in contrast to the increase of the dose-squared term may be an indication of a fundamental difference in the formation processes of the linear and dose-squared components [3, 5, 6]. Fig. 1 Dose-response curves for the yield of radiation-induced dicentric chromosomes (x-rays, 150 kV) in human peripheral blood lymphocytes seen in interphase under PCC conditions after fusion delay times of t D = 0 h ( c ) and t D = 8 h ( a ) [3] and in first metaphase after PHA stimulation ( D from [4], B from new experiments, R. P. Virsik-Peuckert) References 1. Moiseenko VV, Edwards AA, Nikjoo N (1996) Modelling the kinetics of chromosome exchange formatio...