Does the repair capacity of skin change with repeated exposure to X-rays?

A sensitive experimental design and data analysis were used to test rigorously whether the repair capacity in the skin of the mouse foot changes during a course of repeated 240 kVp X-ray doses. Any such changes might reflect saturation or induction of repair enzymes resulting from progressive radiation damage, but most importantly this assumption of equal effect per dose fraction is central to all analyses of multiple-fraction radiation treatments, and remained to be demonstrated conclusively in skin. An X-ray dose of 2.5 Gy was given two, eight, 14 or 20 times with an interfraction interval of 8 h. Individual skin reactions for each mouse were analysed separately, giving 139 estimates of the effectiveness of 2.5 Gy (approximately 35 in each of the four fractionation schedules). Regression analysis of effect per fraction versus number of fractions showed that there was no significant trend, i.e. the damage per fraction was constant regardless of the number of fractions used. The mean damage per fraction was 3.75 +/- 0.15 per cent (95 per cent CL) of the full underlying damage equivalent to transient moist desquamation, and the slope of this plot was 0.0075 per cent +/- 0.022 per cent (95 per cent CL) per fraction. It was concluded that the assumption of equal effect per fraction was not invalidated in mouse skin. Shorter interfraction intervals would not allow full repair between fractions, and this could be misinterpreted as a progressive loss of repair capacity in this type of experiment. This was tested in skin by giving 2.5 Gy doses two, eight and 14 times with a 1-h interfraction interval. Effect per fraction increased with number of fractions, by an extra 37 per cent from two to eight fractions and by a further 14 per cent from eight to 14 fractions, giving the illusion of loss of repair as predicted. This confirms the need to check that where loss of repair capacity is suspected, this is not due artifactually to incomplete repair between fractions in slowly repairing systems.