RELATIONSHIP BETWEEN TUMOR RESPONSE AND THE RATIO OF NUCLEOTIDE TRIPHOSPHATES TO INORGANIC-PHOSPHATE IN SMALL-CELL LUNG-CANCER XENOGRAFTS

We examined whether grossly similar tumor responses, obtained by diffe rent therapies, induce similar patterns of change in the ratios of nuc leotide triphosphate (NTP) to inorganic phosphate (P-i) in two human t umor lines, derived from the tumor of the same patient. The tumor resp onses were induced by doxorubicin 10 mg/kg i.p. or 5 Gy X-radiation in the human small cell lung cancer (SCLC) lines 54A and 54B, grown as x enografts in athymic nude mice. In vivo P-31 magnetic resonance spectr oscopy of tumors was performed pretherapeutically, and on days 1, 4, 8 , and 15 following therapy, in a 4.7 T magnet. Individual NTP/P-i rati os were calculated relative to the pretherapeutic values, and treated (n=28) versus controls (n=28) were compared. In both tumor lines, doxo rubicin induced a significant drop in NTP/P-i at day 1. In 54A tumors 5 Gy induced a significant increase in NTP/P-i, whereas no difference between the NTP/P-i of irradiated and controls was found in 54B tumors . Thus three distinct NTP/P-i patterns were observed in tumors during response to therapy: (i) A decrease, (ii) an increase, and (iii) no ch ange. Our findings indicate that changes in this ratio do not correlat e independently with tumor response in the SCLC sublines 54A and 54B.