It has been pointed out by Little, Strong, and others that one of the basic weaknesses of the early work in the experimental study of the genetics of neoplasms occurring in mice was that the animal strains used were not of sufficient purity. This objection was met by the long and tedious process of close inbreeding of various stocks coupled with careful tabulation of all tendency to the spontaneous development of neoplasms. As a result lines were produced, on the one hand, which gave as high as 80 to 90 per cent of tumors of the mammary gland, and on the other, such a line as C57, which apparently failed to develop a mammary tumor in ten years of inbreeding. The work of the present writers has been largely with the so-called “non-tumor” or “low-tumor” strains, and their results lead them to conclude that the process of inbreeding alone does not insure a strain free from a tendency to produce spontaneous cancer. Unless some way is devised to make it possible to distinguish those individuals whose constitution is favorable to the spontaneous formation of neoplasms they may remain undetected from one generation to another. Recently we have applied a method to this problem which has successfully located female mice with spontaneous, fully developed mammary carcinoma even in such a “low-tumor” strain as C57 (1, 2). We refer to the so-called “functional test” in which female mice are bred rapidly, starting at an early age, and are not allowed to nurse their young. This procedure subjects the females to a prolonged, vigorous hormonal stimulation of the mammary gland, mainly ovarian, coupled with irritation of the epithelium of the gland due to retained secretions within the ducts. This procedure results apparently in an early “aging” effect upon the breeding females, so that mammary gland tumors may arise in animals only four to six months of age. This method has made it possible to locate female mice with cancer when they are still fertile, so that offspring may be obtained either from them or from their close relations. Conversely the same procedure has resulted in making it possible to detect, at a relatively early age, females whose constitution is apparently resistant to the formation of mammary neoplasms under the conditions of our experiment.
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Bagg et al. (1937) studied this question.