Tumour Induction in Rat Skin by 300-kV X-Rays and 15-MeV Neutrons

A transplantation technique was developed to study the carcinogenic action of fast neutrons and X-rays on rat skin without interference from damage produced by the same radiations in underlying tissues, blood vessels and regulating systems, including immunological defenses, of the organism. After whole-body irradiation of inbred white WAG/Rij rats, circular pieces of skin (about 20 mm in diameter) were cut from the backs of the rats. These pieces of skin were transplanted onto the backs of unirradiated brown (WAG/Rij x BN/Bi)F1 hybrid rats in which a graft bed was prepared by excision of similar pieces of skin. The difference in colour easily distinguished the grafted skin from the host skin. Immunological complications are avoided by this choice of graft and host. During the first 14 days after transplantation little difference is observed macroscopically and microscopically between unirradiated skin and skin grafts irradiated with doses of up to 3000 rads of X-rays and 1500 rads of neutrons with respect to healing the graft. After about 14 days the irradiated skin grafts start to decrease in size. After about 8 weeks the ratios of remaining areas of grafted skins relative to controls approach constant values. The skin areas are left in place until the end of the life span of the host. They can subsequently be transplanted onto new hosts and studied for time intervals which exceed the life span of the hosts. Tumours have been observed only at doses which are so large that only few epithelial cells would be expected to retain the capacity for unlimited proliferation. The tumours which occurred have been transplanted in WAG/Rij rats, BN/Bi rats and in F1 hybrids. The tumours grew only in WAG/Rij rats and F1 hybrids, which shows that the basal cell carcinomas observed originated from the cells of the transplanted pieces of skin. The relation of the probability of malignant transformation and loss of cell reproductive integrity is discussed quantitatively. (author)