MODIFICATION OF RUNT DISEASE 



371 



with a series of three homologous spleen and thymus cell injections 

 over a one-week period, will render mice specifically more 

 susceptible to transplantable tumours of donor origin transferred 

 two or more weeks following treatment (Uphoff, 1961). This 

 phenomenon has been interpreted as a form of true "immuno- 

 logical tolerance". There are also other recent reports of the 

 depressant effect on the homograft reaction of continued admini- 

 stration of this compound (see Blumenstock et ah, 1961; and 

 Humphreys et ah, 1961). 



Our results with this drug have been striking. Initial toxicity 

 tests were done, again with three equal doses given subcutaneously 

 to newborn C57BL/6 mice on the first, third and fifth days of hfe. 

 Three doses as small as 0-75 mg./kg. resulted in a one hundred 

 per cent mortality. 



With half of this dose (0-37 mg./kg.) 2 of a test group of 14 

 animals died, one on the fourteenth and one on the twenty-sixth 

 day. The remaining animals developed somewhat more slowly 

 for about the first month, but they promptly recovered 

 with no obvious residual effects except for a distinct greying of 

 the hair, particularly noticeable over the ventral surface. Eight of 

 these animals were grafted with DBA/ 1 skin at about six weeks of 

 age. All of these grafts were fully rejected by the eleventh day. 



Table I 



All untreated runts received in excess of 5 million DBA/i spleen cells neonatally. 

 Potential runts treated with amethopterin received more than 15 million DBA/i spleen 

 cells. The survivors were later grafted with DBA/i skin. Skin graft survival of more than 

 15 days was considered to indicate some degree of tolerance. Survival of more than 30 

 days was designated a "high degree" of tolerance. 



