Ill VIRUSES AND CANCER 853 



Miihlbock, 1956). In Miihlbock's studies the agent-free tumors occurring in mice 

 bearing pituitary grafts were histologically similar to those associated with the 

 agent. 



Since agent-induced chicken tumors may pass through a non-filterable (masked) 

 phase (Bryan et al., 1955), it has been suggested that negative results do not 

 constitute proof that a filterable agent is not involved (Beard et al., 1955). How- 

 ever, since a simple method provides evidence for the mammary tumor agent 

 without difficulty, and since a "non-filterable" phase for the mammary tumor 

 agent has not been demonstrated, it is reasonable to assume tentatively that these 

 "agent-free" tumors lack an inciting agent which is present in other mammary 

 neoplasms of the mouse. 



(c) Alouse leukemia 



Mouse leukemia occurs spontaneously in high leukemia strains (MacDowell 

 and Richter, 1935) and can be induced in certain "low-leukemia" stocks by the 

 administration of either X-rays (Furth and Furth, 1936, Kaplan, 1947), estrogens 

 (Gardner et al., 1940) or carcinogenic hydrocarbons (Mider and Morton, 1939) 

 (Figs. 42-45). Gross (1951) reported the induction of leukemia in low-leukemia 

 stocks by the injection into the newborns of extracts derived either from leukemic 

 tissues or embryos of high leukemia strains. Age at time of inoculation, as well as 

 genetic constitution is important in determining susceptibility to viral induction 

 of leukemia. 



The relationship of X-ray, estrogen and carcinogen-induced leukemogenesis to 

 viral induction has not been elucidated. Although the C3H strain, which Gross 

 has used primarily as a "low-leukemia strain" for induction, is considered to be 

 virus-free, it is susceptible to the induction of leukemia by either X-rays (Kirsch- 

 baum and Mixer, 1947; Gross, 1957) or estrogenic hormone (Gardner et al., 1940). 

 Although the specific line of C3H mice may be important in considering leuke- 

 mogenesis, it has been found that if C3H mice of the Bittner subline (used by Gross) 

 are observed carefully throughout life, leukemia (and other lymphocytic neoplas- 

 tic disease) occurs spontaneously after 15 months of age (Ida et al., 1957), when 

 many investigators (Furth et al., 1956) terminate their experiments. 



Is the "virus" of mouse leukemia an accelerating factor, operating in the same fashion 

 as the mammary tumor agent? It appears that leukemia appears earlier when mice are 

 inoculated with extracts of leukemic tissue at birth. The need for inoculating early in life 

 has raised the question concerning the similarity of the leukemia agent to the "transforming 

 principle" of Lederberg (1956). In a majority of cases, leukemia occvirring in mice injected 

 as newborns is genetically of the same type as the recipient (Gross, 1950; Furth et al., 1956; 

 Ida et al., 1957). However, in some cases the genetic type is that of the donor whose leukemic 

 tissue was extracted (Furth et al., 1956), suggesting that a factor extracted from the leukemic 

 tissue genetically altered cells of the inoculated newborn which not only developed leukemia, 

 but acquired histocompatibility genie determinants of the donor. 



Fig. 41. Section of mouse mammary cancer induced by methylcholanthrene. Centrally 

 in this photo the histologic type is adenocarcinoma. In the upper left, and to the right, 

 keratinized squamous epitheliuna (k) is present. This type of epithelium is characteristic 

 of portions of the carcinogen-induced mammary neoplasm. X 75 



Literature p. Hyo 



