PROBLEMS CONCERNING THE TUMOR VIRUSES 329 



noninfectious papillomas elicited antibodies in rabbits after they had received 

 the material intraperitoneally; this antigenic activity suggested the presence 

 of virus in papillomas, but in amounts too small to produce new papillomas. 

 Next, smaller quantities of virus were exposed in papillomas through the use 

 of procedures which increased the chance of virus survival at the site of 

 inoculation. It was also found that, at times, immune serum could diffuse into 

 the papillomas and combine with the virus. While these experiments showed 

 that small quantities of active virus were present in some induced papillomas, 

 other papillomas failed to yield virus and remained free of antibodies. These 

 latter tumors could have contained insufficient virus to produce tumors when 

 they were assayed by the inoculation technique. 



Serial passage of the virus through domestic rabbits supplied indirect 

 evidence of virus survival in them. Shope (1935) was able to carry the virus 

 from a cottontail papilloma through 14 successive passages in domestic 

 rabbits. Selbie and Robinson (1947, 1948) and Selbie et al. (1948) also reported 

 14 passage generations of the virus in domestic rabbits. Of special interest 

 was the finding that, after passages through domestic rabbits, their virus 

 failed to provoke papillomas in cottontails. The inability of the virus to 

 infect cottontails after exposure to domestic rabbit tissues recalls Duran- 

 Reynals' (1953) observation that a variant of the Rous virus, following 

 residence in the duck, failed to produce the typical sarcoma when brought 

 back to its natural chicken host. 



Despite these suggestive findings, a variant of the virus which is perman- 

 ently adapted to the domestic rabbit was not made available. The virus 

 appears to be resistant to modification, a property which is in keeping with its 

 known resistance to chemical and physical agents and its apparent specificity 

 for the epidermis. Perhaps the problem should be attacked through a modifi- 

 cation of the host's response to infection. Ginder (1952) describes the 

 "dramatic changes" occurring when chemicals are applied to the skin of the 

 domestic rabbit. Intravenous adrninistration of the virus to rabbits bearing 

 tar-induced papillomas accelerates the growth of the lesions and the applica- 

 tion of carcinogenic compounds to the papillomas hastens the change to 

 malignancy. Procedures known to alter the susceptibility of the host to virus 

 infections or to the growth of tumors, such as radiation, administration of 

 cortisone, or the methodology for the production of acquired tolerance, may 

 bring about a change in the cottontail virus which will enable it to grow 

 indefinitely in the skin of the domestic rabbit. 



Those familiar with the mammary tumor virus of mice will recognize 

 similarities and dissimilarities between it and the virus of rabbit papillo- 

 matosis. The mouse virus will be discussed later, but it is apropos at this time 

 to mention that inbred mice exhibit pronounced variations in susceptibility 

 to it. When strains of mice that do not carry the virus are exposed to it, some 



