Tumor growth retardation and pathophysiological effects of adenosine 5′‐triphosphate therapy measured by thallium washout, ³¹P nuclear magnetic resonance, laser doppler flowmetry, and intradermal angiogenesis

Abstract

SUMMARY Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with inmperitoneal (i.p.) adenosine 5'-triphosphate (ATP) were studied in vitro, and in vivo in both C3H and ndnu mice. In vivo daily ATP treatments caused a small dose-dependent reduction in the total neovascular lumen area and thallium washout. There was an associated reduction in tumor volume doubling time but a similar growth rate reduction was also seen in vitro where flow has no impact. Daily ATP treatments at the maximally tolerated dose (2 mmoVkg i.p.) did not significantly affect the pH nuclear magnetic resonance or the phosphocreatine/inorganic phosphate (PCr/P,), PATP/P, or phosphomonoester (PME)/ PATP ratios. The acute systemic physiological effects of i.p. ATP were mild, consisting of a transient reduction in skin laser Doppler flow and mean arterial pressure. Systemic toxicities of ATP given as daily boluses at doses capable of producing significant growth retardation of FSaII tumors were transient. Our results are most consistent with the hypothesis that the growth retarding effects of ATP are primarily a result of a decreased proliferation rather than tumor cytotoxicity or systemic pathophysiology. The main toxicity of ATP at active dose levels is cardiovascular. ATP might be useful as a biological modifier of chemotherapy or radiation.

Effect of Intraperitoneal ATP on Tumor Growth and Bone Marrow Radiation Tolerance

“…neurologic (10, Il), and muscular functions (4). Recently, we presented evidence that ATP can slow the growth of a murine mesenchymal tumor, and that the effect was unlikely to be due to physiological alterations ( 12). In the present report we examined the differential effect of ATP between tumor and bone marrow.…”

Tumor Growth and Tumor Radiosensitivity in Mice Given Myeloprotective Doses of Fibroblast Growth Factors

“…The following three murine tumors syngeneic to C3H/HeN mice were used in these experiments: one squamous cell carcinoma (SCC-VII) and two sarcomas (KHT and Rif-1). Single-cell suspensions of excised tumors were prepared as described previously (12). The cell viability, evaluated by trypan blue dye exclusion, was greater than 85% for each type of tumor.…”