This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Williams, A. D. Articles by Winzler, R. J. Search for Related Content PubMed PubMed Citation Articles by Williams, A. D. Articles by Winzler, R. J.

The Effect of A-Methopterin on Formate-C¹⁴ Incorporation by Mouse Leukemias In Vitro^*

Albert D. Williams, Grant G. Slater and Richard J. Winzler

( Departments of Biological Chemistry, University of Illinois College of Medicine, Chicago, Illinois, and of Biochemistry and Nutrition, University of Southern California, Los Angeles, Calif.)

The in vitro incorporation of formate-C¹⁴ into the protein and lipids of several leukemic mouse tissues and of normal mouse liver has been studied. The folic acid analog, A-methopterin, has been shown to inhibit by 72 per cent the incorporation of formate-C¹⁴ into the protein of leukemic cells sensitive in vivo to A-methopterin. A-methopterin inhibited by 40 per cent the incorporation of the isotope into the proteins of a lymphoma resistant in vivo to A-methopterin therapy. There was no significant effect of A-methopterin on the incorporation of formate-C¹⁴ into the gross protein fraction of normal mouse liver.

The protein residue from the L1210-S lymphoma incubated in the presence and absence of A-methopterin was further fractionated to isolated pure methionine, serine, adenine, and guanine. Serine had the highest specific activity, with the purines having about 40 per cent as much activity as serine, and methionine about one-third of the activity of the purines. The inhibitory effect of A-methopterin on the incorporation of formate-C¹⁴ into ribonucleic acid purines was significantly greater than its effect on incorporation into serine and methionine.

^* This work was supported by a grant from the National Institutes of Health of the United States Public Health Service.

Present address: Institute for Medical Research, Cedars of Lebanon Hospital, Los Angeles, Calif.

Received 4/11/55.