The Design and Interpretation of ‘Top-up’ Experiments to Investigate the Effects of Low Radiation Doses

Summary

The experimental design consisting of a partial tolerance dose followed by a top-up dose, is used as a method of comparing the effects of different radiations and irradiation schedules in vivo. It complements the usual approach of giving multiple equal fractions of a single radiation type to obtain an iso-effect, as it enables low doses per fraction to be studied without the need to use a large number of fractions or a long overall time. For normal tissues in animals, the effect of X-ray doses as low as 0·1 Gy per fraction can be detected when given as 20–40 fractions followed by a top-up dose of neutrons. In order to minimize variations in the effect of the top-up dose, neutrons are used as a top-up radiation in preference to X-rays.

The methods of implementing this approach are explained in detail. Analysis of the data is described, with emphasis on the Linear Quadratic model of radiation dose-fractionation. However, it is not necessary to adopt this or any particular mathematical model in order to intercompare directly the effects of different radiations or irradiation schedules using the top-up approach. Such models nevertheless simplify the design of top-up experiments. Whilst any type of radiation can in principle be used as the top-up, this is given optimally as a dose of fast neutrons split into two fractions.

• top-up experiments
• fractionation
• neutrons
• low doses