The Use of ‘Top-up’ Experiments to Investigate the Effect of Very Small Doses Per Fraction in Mouse Skin

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Abstract
The partial tolerance type of ‘top-up’ experiment has been investigated to determine the resolution of this approach for studying the damage to mouse skin from very small doses of X-rays and neutrons. The effect of 20 fractions, each as small as 0·10 Gy of X-rays or of 0·05 Gy of neutrons, can be detected if 3 MeV neutrons are used as the ‘top-up’ reference radiation. This capability results from the almost linear underlying dose-response curve and highly reproducible dose-effect relationship for the low energy neutrons. The data fit the linear quadratic model of dose fractionation for X-rays down to fractional doses of 0·75 Gy, but at lower doses there is a trend towards an increase in the skin radiosensitivity. Modelling shows that this might be consistent with a sub-population of the cells showing an exceptional radiosensitivity, and a replenishment of this subpopulation occurring in the 8 h between small dose fractions. More experiments are needed at very low doses in order to confirm this hypothesis for skin and for other tissues.

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