Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice.
Intraperitoneal injections of adenosine 5'-monophosphate (AMP) or adenosine 5'-triphosphate (ATP), but not of adenosine, inorganic phosphate or pyrophosphate, were shown to inhibit tumor growth and host weight loss in tumor-bearing murine hosts. The inhibition of tumor growth and host weight loss did not exhibit a cause-effect relationship, though both were mediated through expansion of red blood cell (RBC) ATP pools which were promoted by administered adenine nucleotides. We then demonstrated that expansion of RBC ATP pools was preceded by expansion of liver ATP pools and that the adenosine precursor for this type of enhanced RBC ATP synthesis originated in the turnover of expanded liver ATP pools. Although adenosine, which is the primary catabolic product of ATP in the peritoneal cavity or the systemic circulation, was sufficient to yield an expansion of mouse liver ATP pools in vivo, external phosphate was required for the subsequent expansion of RBC ATP pools, which in turn produced elevated extracellular (blood plasma) ATP levels. The anticancer activities which correlate with the elevated blood plasma ATP concentrations are proposed to be the result of direct action of extracellular ATP on the tumor and host tissues.
Rapaport
E
E
Department of Microbiology, Boston University School of Medicine, MA 02118.
Fontaine
J
J
D000255:Adenosine Triphosphate / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015431:Weight Loss / Q000187:drug effects*
D000255:Adenosine Triphosphate