Direct demonstration of the active salvage of preformed purines by murine tumors.
The purine de novo biosynthetic pathway has become a target for chemotherapeutic agents and because of the possible contribution of the salvage of extracellular purines to cellular purine pools an examination of the ability of mouse tumors in vivo to exploit the salvage pathways was undertaken. Our data reveal that circulating radiolabeled preformed purines are rapidly and actively salvaged in both normal liver and in two different types of model tumors. The salvaged purines were found to be distributed between both acid soluble cytoplasmic purines and acid insoluble nucleic acid associated purine species. The ability to salvage adenine, the most abundant circulating purine in C57BL/6 mice, was highest in normal liver with the two different model tumors demonstrating lower specific activities of salvaged acid soluble purines. The amount of radiolabel incorporated into acid insoluble nucleic acid was dependent upon the tumor type. Because of the active salvage observed in these tumors, the mechanism by which de novo purine biosynthesis inhibitors serve as effective chemotherapeutic agents may be more complex than simple biosynthetic inhibition.
Johnson
D L
DL
Department of Chemistry, Pennsylvania State University, University Park 16802.
Mullin
R J
RJ
Duch
D S
DS
Benkovic
S J
SJ
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011687:Purines / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011687:Purines; D004247:DNA