ENERGETICS OF NUTRITION AND POLYAMINE-RELATED TUMOR-GROWTH ALTERATIONS IN EXPERIMENTAL CANCER

The aim of this study was to evaluate whether food intake modulates ex perimental tumour growth by acute alterations in the energy state and blood flow of the tumour, and if so whether such changes are related t o alterations in the enzyme ornithinedecarboxylase (ODC) and DNA synth esis. Inbred mice (C57BL/J) bearing a syngeneic undifferentiated and r apidly growing tumour were used. The tumour levels of high energy phos phates were measured in vivo by P-31-NMR spectroscopy and biochemicall y following tissue extraction. DNA synthesis was estimated by measurin g the incorporation of bromodeoxy-uridine into tumour DNA. Difluoro-me thylornithine (DFMO) was used to inhibit ODC-activity. Tumour blood fl ow was estimated by a Xe-132 local clearance technique. Tumour progres sion was associated with a significant decrease in tumour tissue high energy phosphates. Acute starvation decreased DNA-synthesis and tumour energy charge as well as its PCr/Pi which were rapidly normalised dur ing subsequent refeeding. These changes were related to similar altera tions in tumour blood flow. The inorganic phosphate (Pi) resonance and the resonances in the phosphomonoester (PME) region were considerably increased in tumour tissue. Inhibition of ODC-activity by DFMO decrea sed DNA-synthesis, which was associated with a secondary increase in t umour high energy phosphates probably due to a lowered energy demand f or tumour cell division. The results demonstrate that host undernutrit ion was translated into retarded tumour growth associated with a decre ase in the energy state and blood flow of the tumour. The results have bearing for the evaluation and planning of all treatment protocols wi th potential influence on food intake in experimental tumour-bearing a nimals.