The Use of Methylcholanthrene-Induced Skin Carcinoma of the Mouse in Radiobiology

Abstract

Over the past several years there has been an increasing interest in the investigation of basic radiobiologic phenomena utilizing experimental animal tumors. The usual test objects are either tumor grafts or common spontaneous tumors of rodents, such as mammary carcinoma, lymphomas, or hepatomas. Tumor grafts introduce the complication of host immunity, which may result in tumor rejection after minimal radiation damage, or even spontaneous regressions (Scott, 6). With spontaneous animal tumors this problem is eliminated and the tumor-host relationship is normal. Most radiocurable cancers in man, however, are squamous-cell carcinomas, and data derived from experimentation with mammary neoplasms or lymphomas can hardly be extrapolated to such growths. It has been known for many years that squamous-cell carcinoma of the skin can be induced in experimental animals by exposure to numerous polycyclic hydrocarbons. One of the most potent of these is 20-methylcholanthrene. Iball (3) demonstrated, in 1939, that skin painting of mice with this agent results in squamous-cell carcinoma after a latent period of a few months in 100 per cent of exposed animals. We are using this neoplasm as a test object in numerous radiobiologic problems such as the study of time-dose relationships, synergistic action between chemical agents and irradiation, the study of radioprotective compounds, and the influence of physical agents such as altered oxygen tension. In the experiment to be described here, we attempted to correlate the percentage control of methylcholanthrene-induced cancers by single exposures to irradiation with data derived from experiments on human cancer cells irradiated in culture (Puck and Marcus, 5). Method CBA male and female mice were used in this experiment. Beginning at an age of approximately six weeks, these animals were exposed to 20-methylcholanthrene. A saturated solution of this chemical in benzene was prepared and applied to a small area of the skin of the back by means of a cotton-tipped applicator. Epilation occurred within one week, after which time further application in the same area was extremely easy without the necessity of tattooing or other skin marking. This procedure was repeated twice weekly until gross evidence of neoplasm of the skin appeared; usually about twenty weeks of application were required. The lesions were then subjected to biopsy to confirm the presence of invasive squamous carcinoma. In a pilot study it was found that the incidence of localized squamous cancers was higher and the latent period shorter in the inbred CBA strain than in random-bred albino Swiss mice receiving an equal number of skin paintings. In control animals the lesions were allowed to progress untreated and without exception caused death within three to four months. About 10 per cent showed lung metastases at autopsy.