The response of mouse skin to irradiation with neutrons from the 62 MV cyclotron at Clatterbridge, U.K.

Acute skin reactions on mouse feet were used to measure the effect of 62 MeV p-Be neutrons from the cyclotron at Clatterbridge, U.K. The results were compared with the response to 16 MeV d-Be neutrons from the cyclotron at Hammersmith, 4 MeV d-Be neutrons from the van de Graaff accelerator at the Gray Laboratory, and 250 kVp X-rays. Up to 16 equal radiation fractions were given alone, or 16 fractions followed by "top-up" doses of 4 MeV d-Be neutrons to study the effect of neutron doses less than 1 Gy per fraction. For equivalent skin reactions, 9-16% more dose (total neutron + gamma) was needed with p(62)-Be neutrons compared with d(16)-Be neutrons. This did not vary significantly between 1 and 16 fractions. The top-up studies indicated that this figure might rise to approximately 14-32% at very low doses of neutrons, the value depending on the method of analysis of the data. The data indicate that the "standard" clinical protocol of 1.47 Gy per fraction (N + gamma dose) in 12 fractions given at Hammersmith with d(16)-Be neutrons would correspond to a dose of 1.64 Gy per fraction (N + gamma) at Clatterbridge using a similar regime of p(62)-Be neutrons. d(4)-Be neutrons were more effective than d(16)-Be neutrons by a factor of 1.6 over the whole range of dose per fraction studied (0.05-14.5 Gy per fraction of d(4)-Be neutrons). Relative to X-rays, the RBE for p(62)-Be neutrons was 1.6 +/- 0.02 for a single X-ray dose of 30 Gy, rising to 2.9 +/- 0.04 for an X-ray dose per fraction of 4.6 Gy given 16 times. The full-course fractionation data and the top-up data together indicate an extrapolated limiting RBE at vanishingly small doses per fraction of 4.2-4.8 depending on the method of analysis. The X-ray data were well-fitted by a linear-quadratic (LQ) model of dose-fractionation, with alpha/beta = 8.6 +/- 1.5 Gy. The LQ model also provides a fairly good description of the neutron responses, alpha/beta being large (greater than 24) reflecting predominantly linear underlying dose-responses for all the neutron beams. This in turn reflects the small variation observed in the relative effectiveness between the 3 neutron beams with changes in dose per fraction.