A number of workers have reported on the effect of aminopterin and A-methopterin on the course of the growth of the Rous sarcoma and certain transmissible tumours in chicks. Woll (1948) and Little, Sampath, Paganelli, Locke and Subbarow (1948) have shown that a number of folic acid antagonists completely or partly inhibit the growth of the Rous chicken sarcoma although some toxic effects were encountered. The latter workers showed that the toxicity of aminopterin, in particular, could be partially neutralized by either pteroyldi-or pteroyltriglutamic acid in a 25 to 1 ratio, but such mixture showed no virusinhibiting effect. Stock, Biesele, Burchenal, Karnofsky, Moore and Sugiura (1950) have also demonstrated that several analogues of folic acid exert an adverse effect upon tumour tissue. Ringsted (1952) fed a balanced chick mash containing aminopterin (5 mg./kg. of food) and found that the survival rate of chicks inoculated with Rous sarcoma was significantly higher at the end of the first week compared with that of chicks receiving no drug. The mean time of first appearance of the tumour in the survivors was also greater in the chicks receiving aminopterin, but the tumour incidence in both the medicated and control groups was 100%. Bessis and Freixa (1950) found that aminopterin and A-methopterin offered partial protection against a transmissible erythroblastosis in young chicks, but some intoxication was encountered. Ringsted (1953) showed that aminopterin in a chick mash at levels of 5, 10, 20 and 40 mg./kg. increased the mean induction time of a Mill Hill endothelioma in young chicks. The two higher levels proved toxic, and the drug at all levels had no effect on the total number of takes and subsequent growth-rate of the tumours. Darcel (1953a) failed to show any increase in the time taken for tumours to appear when aminopterin or A-methopterin were given orally to chicks bearing tumour strain RPL 12. The drugs were administered directly into the crop in aqueous suspensions (0.1 and 1.0 mg. of each drug/day). No toxic symptoms were reported.Recently, citrovorum factor, a substance closely related to folic acid, has been found to be many times more effective than folic acid itself in reversing the toxicity of folic acid antagonists in the rat, chick, and man, and in this paper a number of observations are presented on the effect of aminopterin, A-methopterin and synthetic citrovorum factor on the growth of transplantable lymphoid tumour strains isolated from cases of avian leukosis.
METHODSThe general characteristics of the tumour strains used in the present study, RPL 12 and 19, have been described by Darcel (1953b). A tumour develops at the site of inoculation followed by rapid metastasis, in the absence of leukaemia, to the viscera, especially the liver.Crossbred (B.R. X Br.L. and B.R. x W.L.) chicks were inoculated with tumour cell suspensions either at two or seven days of age. The birds were maintained in small metal cages and fed freely on a balanced chick mash.The tumour cell suspensions were prepa...