PROBLEMS CONCERNING THE TUMOR VIRUSES 315 



1. Host-Virus Relationships 



Many factors are known to be involved in the interactions between the 

 Rous sarcoma virus and its hosts but, in recent years, the age factor has 

 probably received most attention. Duran-Reynals (1953) has emphasized the 

 importance of age in the response of the host to a number of tumor viruses and 

 has used the virus of Rous sarcoma extensively in his investigations. He 

 (Duran-Reynals, 1940a) observed that administration of the virus to chicks 

 produced hemorrhagic areas around small blood vessels because non-neoplastic 

 lesions developed in the vessels and these lesions contained abundant virus. 

 With advancing age, chickens became more resistant to the virus which, 

 instead of provoking "destructive" lesions, induced cell proliferation that 

 proceeded to malignancy. Likewise, young animals responded to small 

 amounts of virus by developing rapidly growing tumors which often metasta- 

 sized, whereas adults required larger quantities of virus before developing 

 tumors that showed less tendency to metastasize. These reactions between 

 host and virus are consistent with those of other virus-induced diseases when 

 age renders the older animals more resistant, but Duran-Reynals considered 

 the age of the host as being of paramount importance in the successful 

 adaptation of the Rous sarcoma virus to other species. 



He found it was impossible to obtain permanent adaptation of the virus 

 when it was transferred from chicks to very young ducks, but adaptation did 

 occur when day-old ducks received the virus from tumor grown in 3- to 10- 

 month-old chickens. Thus, the age of the inoculated duck and the age of the 

 host chicken supplying the virus were the important factors in successful 

 adaptation of the virus to a heterologous host. Duran-Reynals interpreted 

 the age factor as playing a far more important role than rendering the young 

 more susceptible, in that the virus, while residing in the older and more 

 resistant chicken, underwent alterations which increased its capacity to 

 infect a foreign host. This concept of the influence of the host's age upon the 

 infectivity of tumor viruses presents a challenging problem to the cancer 

 investigator because if it can be applied successfully to other tumor viruses, 

 especially to those not previously exposed to many passages in the laboratory, 

 it could offer an explanation for the induction of different types of cancer by 

 a single virus. 



It has been known for years that the age of the host is important in its 

 response to virus infections and all reviews of the tumor viruses emphasize 

 the importance of the age factor, particularly in relation to successful efforts 

 at heteroinoculation of the Rous virus (Andervont, 1957). While the varia- 

 bility and adaptability of the virus must be of importance in its ability to 

 evoke responses in its hosts, some of the most recent work suggests strongly 

 that such responses can be conditioned by the quantity of virus used as 

 inocula. Bryan (1957), in a recent summation of the host-virus relationships of 



