PROBLEMS CONCERNING THE TUMOR VIRUSES 337 



virus and its hosts were found to be so different from those of most known 

 tumor viruses that the scope of virus-induced tumors could be enlarged to 

 include almost all tumors. 



Cancer of the mammary gland in mice had been studied intensively for 

 many years. It was the tumor of choice because its external location made 

 detection easy and it occurred frequently in a common laboratory animal. 

 Its tendency to grow progressively, to recur after incomplete removal, and to 

 metastasize established it as a malignant tumor (Dunn, 1953). The fact that 

 a mammalian tumor of common occurrence had been characterized as a 

 malignant neoplasm before a virus was implicated in its origin made a 

 profound impression upon cancer workers. This was the first major contribu- 

 tion of the virus to the cancer problem. 



Before the discovery of the virus, the occurrence of breast cancer in mice 

 was known to be dependent upon the susceptibility of the animal and the 

 effects of hormonal stimulation. The relative importance of these factors was 

 difficult to ascertain and, to provide suitable test animals, inbred strains of 

 mice were established to fulfill the requirements of controlled genetic investi- 

 gations. Through the process of selection, strains were procured which 

 showed high or low incidences of breast tumors. When reciprocal breeding 

 between such strains was carried out by the staff of the Roscoe B. Jackson 

 Memorial Laboratory (1933) and by Korteweg (1934), it was found that mice 

 born to high-tumor strain mothers developed mammary cancers while those 

 born to low-tumor strain mothers did not. This showed that the maternal 

 parent was largely responsible for the occurrence of tumors in the offspring; 

 by foster-nursing procedures, Bittner (1936) found that mother's milk 

 contained an agent which was responsible for the production of tumors. For 

 the purpose of this discussion it is essential to note that discovery of this 

 virus followed the development of inbred strains of mice showing extreme 

 variations in their susceptibilities to the development of breast cancer. 

 Briefly, discovery of the virus was a by-product of an effort to ascertain the 

 influence of the host upon the occurrence of this tumor. 



The importance of this virus as a member of the tumor viruses has been 

 emphasized repeatedly by every investigator who has reviewed the subject 

 since 1936. The entire problem of mammary cancer in mice was presented in 

 a symposium (1945) by members of the staff of the National Cancer Institute. 

 Other reviews dealing specifically with the problem have been prepared by 

 Bittner (1948, 1955, 1957a), Andervont (1946, 1949a, 1955), and Dmochowski 

 (1953a, 1957). The reader is referred to these earlier summations for details of 

 work with the virus. This discussion will include those facets of the problem 

 which are receiving most attention and, for the most part, only recent 

 publications. Almost all experiments with this tumor involved studies of the 

 host-virus relationships and, although it is impossible to draw clear lines of 



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