A recent review of the literature on time-dose relationships (1) suggested the possibility of improving the results of radiation therapy in certain circumstances by optimum timing of the individual treatments in a series. This particular aspect of the time factor is based on the theory that there are radiosensitive and radioresistant periods during the overall time of treatment, occurring as a result of temporary arrest of mitosis by irradiation. Since cells are most sensitive during mitosis, this period of arrest is a radioresistant period and radiation given during this time would be relatively ineffective; if irradiation were delayed until resumption of mitosis, it would fall into a radiosensitive period and produce a correspondingly greater effect. This theory was explored by Koller and Smithers (3) in a clinical experiment in which they took serial biopsies of six skin carcinomas during the treatment course and adjusted their treatment accordingly; that is, if they found no or few cells in mitosis they delayed treatment, but if they found many cells in mitosis they gave a treatment. In this way they were able to obtain good results with lower doses than they had used with daily treatment. Since this procedure is not practical in routine radiotherapy, it was decided to test the possibility of finding a predetermined fractionation plan which would fit a sufficient number of tumor-bearing individuals so that a better response for the group as a whole would be obtained. This had been tried for three types of tumors by Sambrook and co-workers (9) and it was their impression that responses differed, but with only 9 patients definite conclusions were difficult. The tumor chosen for this study is the spontaneous mammary adenocarcinoma of C3H mice. The mice were obtained from the Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, and later, when it was unable to supply sufficient numbers, from the Cumberland View Farms in Tennessee. No differences were observed between the two groups. The mice were kept in stainless steel cages containing cedar shavings. They were fed Purina Laboratory Chow and had free access to water at all times. They were usually kept about ten days after arrival to become accustomed to their new enviromnent before treatment was begun, but in a few instances mice with larger tumors were treated four days after arrival. In order to minimize “cage effects” (8), equal numbers of mice from groups being compared were kept in the same cage. An attempt was made to have the tumors of as nearly the same size as possible. The mice were identified by cage number, location of tumor, and sometimes by clipping the hair from one leg. Treatment plans were assigned by selecting a mouse, shuffling the record cards, and choosing a card at random. Several means of immobilizing the mice for treatment were tried and a method was devised which proved practical.
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Sault et al. (1958) studied this question.