370 PAUL S. RUSSELL 



doses required for best results involve a high incidence of toxic 

 reactions in the treated recipients. 



Preliminary observations of a few normal C57BL/6 mice given 

 subcutaneous injections of B.W. 57-322 on the first, third and 

 fifth days of life indicated that almost all animals receiving as 

 much as 25 mg./kg. on each of these days were dead by the tenth 

 day of life. 



Toxicity on a similar dosage schedule with 12 mg./kg. or less 

 was considerably milder with all animals surviving after treatment 

 with 3 mg./kg. Five animals were thus treated with three injec- 

 tions of 15 mg./kg. and seven with 3 mg./kg. of this drug after 

 neonatal injections of 19 million DBA/i spleen cells. No delay in 

 onset of runt disease or amelioration of its severity was observed 

 as compared with control animals of the same litters. All were 

 dead by the twelfth day. A similar series of injections of 1-5 

 mg./kg. also failed to influence the disease. 



(4) Amcthopterin (methotrexate; 4-amino-N^^-methylpteroyl- 

 glutamic acid). This antifolic acid compound has proven to be 

 of use in the treatment of certain leukaemias and other malignant 

 diseases. Its effect on the inductive phase of serological antibody 

 production has been reported to be slight (Nathan et at., 1961) 

 although aminopterin, another folic acid antagonist, has been 

 found to suppress antibody production appreciably (Sterzl, 1961). 



Uphoff (1958) has found this compound to be capable of 

 procuring a considerable increase in the percentage of mice 

 surviving the delayed reaction following lethal whole-body 

 irradiation and subsequent infusion of adult homologous bone 

 marrow. She used a series of nine intraperitoneal or subcutaneous 

 injections giving doses of 3-0 mg./kg. or 1-5 mg./kg. at each 

 injection. Fairly severe drug toxicity occurred with these 

 treatments and was more marked in females, as previously ob- 

 served by others (Goldin et al, 1950). 



Very recently she has extended these observations by demon- 

 strating that a similar course of amethopterin treatment, combined 



