A Study of the Development of Mammary Tumours in Hybrid Mice

THE test mice most commonly used for ascertaining the presence of the mammary tumour agent are susceptible hybrid female mice obtained by mating low-breast-cancer-strain females to high-breast-cancer-strain males. In these test mice a low incidence of spontaneous mammary tumours was frequently and was frequently found to be higher than that of their maternal parents (Andervont, 1945a). Of even greater interest was the high tumour incidence reported in the progeny of susceptible low-cancer-strain females mated to high-cancer-strain males which had been subjected to forced breeding-that is, bearing a number of litters in quick succession (Andervont, 1945b). A similar high incidence of breast cancer was also observed in forcibly-bred hybrid progeny of low-cancer-strain females of low susceptibility to breast tumours mated to high-cancer-strain males (Bagg and Jacksen, 1937; Strong, 1943). Attempts to discover the mammary tumour agent in mammary tumours of some of these hybrids proved unsuccessful (Andervont, 1945b). A number of possibilities was suggested (Andervont and Dunn, 1949) to explain the appearance of breast cancer in hybrid females: presence of a weak agent or small quantities of it or even a different agent in low-cancer-strain female mice; transmission of the agent from the male parent or influence of the more susceptible genetic constitution of this parent; hormonal stimulation overcoming the absence or small quantities of the agent; contamination; even de novo origin of the agent. In connection with the initially recorded observations on tumours in hybrid mice, an investigation was carried out in an attempt to obtain a high incidence of mammary tumours in hybrid mice bred in the laboratory, with a view to ascertaining the respective parts played by genetic constitution, hormonal stimulation, and the agent in the development of mammary cancer in these mice, obtained by mating C57 Black low-cancer-strain females of low susceptibility to the agent to RIII agent-harbouring high-cancer-strain males. It was also planned to study the inheritance of mammary tumours in the progeny of these hybrid females obtained by brother-to-sister matings. Preliminary findings of this study have already been reported Biological tests for the presence of the agent in some of these tumours as well as a study of the microscopical appearance of breast cancer in these mice are now complete, and a full account of this investigation is now possible. During the intervening years, since the present