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.

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