Ill VIRUSES AND CANCER 857 



be introduced soon after birth, whereas for mammary cancer this is not so impor- 

 tant, although relatively young mice are more susceptible than older animals. 



No evidence has been obtained to demonstrate an immunologic basis for the 

 resistance of older animals to mouse tumor agents {e.g. mammary tumor). Heterol- 

 ogous hosts develop antibodies which inactivate the Bittner agent (Andervont 

 and Bryan, 1944), but antigenicity varies with genetic type of mouse host serving 

 as the source of agent (Bittner and Imagawa, 1955), suggesting that a tissue antigen 

 is associated with the agent. Similar observations have been made with chicken 

 tumors (Beard et al., 1955). Antisera have failed to inhibit mammary cancer 

 development in high tumor strains which obtain the milk agent by nursing (Bittner, 

 1948). 



In the case of the chicken tumors, inactivating antibodies are generated by the 

 host (Duran-Reynals, 1940). That these are specific, however, is open to question, 

 since they occur spontaneously in animals whose exposure to the agent is unlikely 

 (Duran-Reynals, 1953). Tissue antigens are separated from viral antigens with 

 difficulty, if at all conclusively. There is cross immunization against the different 

 chicken tumor viruses (Burmester and Belding, 1947). 



Duran-Reynals (1953) believed that the chicken tumor agents are analagous to 

 the viruses responsible for the common infectious diseases. Newly-hatched chicks 

 develop a hemorrhagic disease and old chickens neither hemorrhagic disease nor 

 neoplasm when the virus is inoculated. The serum of chicks, in contrast to serum 

 of old chickens, does not inactivate the virus of Rous sarcoma. The development 

 of a neoplasm according to Duran-Reynals, is correlated with an intermediate 

 immunologic status. 



The immune bodies in the serum might be evidence of a latent infection, which 

 may manifest itself by the appearance of a neoplasm. When chickens of flocks in 

 which leukosis appears spontaneously have been isolated during hatching and 

 rearing, they have remained free of the disease (Burmester, 1957); those which 

 develop leukosis may have obtained the infection b\^ way of the egg. Tracheal and 

 nasal washings of infected birds may transmit lymphomatosis. Birds reared in 

 isolation do not have antibodies against the Rous virus, but possess them after 

 immunization with lymphomatosis. 



Cancerous cells (c) have invaded beneath the muscularis mucosae, (m). The squamous 



epithelium is designated by "e", the normal glandular tissue by "g". x 45 



Fig. 48. Squamous cell carcinoma of the mouse skin. This tumor was induced by methyl- 



cholanthrene. Stroma is designated by "s", the keratinized epithelium by "e" and "k". X 45 



Fig. 49. Mitotic figure in a hepatoma cell, x 600 



Fig. 50. Pulmonary tumor induced in lung grafted to the ear. "i" designates normal lung, 



"t" the pulmonary tumor which is similar to that seen in Fig. 54, and "s" the skin of the 



ear within which the lung tissue graft had been made. Since pulmonary tissue from parent 



strains either susceptible or resistant to the induction of such tumors can be grafted into Fi 



hybrids, which are susceptible, it is possible to test intrinsic susceptibility of the lung from 



"susceptible" and "resistant" strains within the same Fi hybrid host to the action of the 



tumor-inducing agent, in this case urethane. x 40 



Fig. 5 1 . Pulmonary tumor induced by the administration of urethane. Such tumors are of 



alveolar origin. X 40 



Literature p. 870 



