The Metabolic Effects of 4-Aminopteroylglutamic Acid in the Guinea-Pig

1945) and reports of its effectiveness in the treatment of the haematological changes of pernicious anaemia were followed by the production of numerous synthetic analogues and derivatives, some of which were shown to be of value in the treatment of leukaemia and allied disorders.The synthesis of a potent substance of this nature, 4-aminopteroylglutamic acid (aminopterin), was announced by Seeger, Smith & Hultquist (1947).Attempts to produce anaemia in animals by inducing folic-acid deficiency in various ways have been reviewed by Girdwood (1950), who refers to the use of 4-aminopteroylglutamic acid for this purpose in mice, rats, chicks, dogs and guinea-pigs.The reports suggest that in animals other than the guinea-pig the substance produces anaemia and leucopenia, and that these changes can be reversed with difficulty by high dosage of pteroylglutamic acid.Minnich & Moore (1948) produced a hypoplastic anaemia and agranulocytosis in guinea-pigs using 4-aminopteroylglutamic acid, but these changes could not be prevented by the simultaneous administration of liver extract or of pteroylglutamic acid.The main purpose of the present investigation was to explore further the possibility of reversing the haematological changes induced by 4-aminopteroylglutamic acid in the guinea-pig, and to assay the livers of the animals for their content of pteroylglutamic acid and of vitamin B12, EXPERIMENTAL Methods empluyed.Various tests were carried out on groups of at least five male guinea-pigs of about equal weight.Each test was controlled by the use of a group of untreated animals.All animals, including the controls, received 20 mg.ascorbic acid daily in solution, given by intraperitoneal injection.When 4-aminopteroylglutamic acid was administered it was given by intraperitoneal injection.All other injections were given intraperitoneally, with the exception of injections of p-aminobenzoic acid which were given into the subcutaneous tissues at the back of the neck.The animals were kept in separate cages with wire-grid bottoms, and were given unlimited amounts of a commercial diet containing a negligible quantity of folic acid.