A study of the influence of spatial distribution of ionization on skin carcinogenesis using proton and alpha-particle bombardment.

Abstract

The relation of the density of ionization to the induction of malignant neoplasms in mouse skin following focal bombardment with various types of heavy high energy charged particles is being investigated. These particles (protons and alpha particles) have a finite, energy-dependent range of penetration in tissue. Ionization occurs throughout the entire path of the particles with a final rise to a peak (Bragg peak) just before the end of the path is reached. By the introduction of a rotating disk filter of varying thickness in the form of a wheel revolving in front of the radiation port, it is possible to irradiate a cylinder of skin with very nearly uniform ionization limited to a depth of 1, 2, or 3 mm, as desired. This makes it possible to deliver the same number of rads to a given volume of tissue in an essentially homogeneous distribution of ionization for a given particle. Comparison of the radiation effects of two or more particles can then be made with references to linear energy transfer and relative biological efficiency. Such factors as threshold, linear, or nonlinear response in radiation carcinogenesis also can be evaluated. In earlier studies (1, 2) it was reported that atypical epithelial hyperplasia developed within twenty days following bombardment of mice with 2,000 rads of either protons (10 MeV) or alpha particles (40 MeV), which at these respective energies penetrate to a depth of only 1 mm. The purpose of the current study was to determine what the fate of these lesions would be if the animals were bombarded with 2,000 rads of each particle and allowed to live for one year, at which time they would be sacrificed and examined microscopically. The question posed was whether such lesions would remain the same during this extended period up to one year post-bombardment, or regress, or conversely progress to malignant neoplasms. This experiment therefore offered an opportunity to determine at the same doses and with essentially uniform ionization what lesions would develop from proton and from alpha-particle bombardment in a given post-bombardment period of time. This, then, would create the possibility of comparing the effect of the difference in density of ionization between two particles at identical doses. Heretofore, no similar investigation of this basic problem in radiation biology had been carried out for heavy high energy charged particles. Three criteria have been established as essential in the experimental design of this program: (a) uniformity of external beam employed for irradiation in reference to particle produced; (b) bombardment with essentially uniform ionization in a given volume of tissue with a limit in tissue depth of irradiation, as desired; and (c) basing of the assessment of effects primarily upon the histopathological findings. Ionization is dosimetrically expressed in terms of rads.