31P NMR study of the impact of dietary manipulation on tumor metabolism and response to methotrexate.
The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty-four hours after nutritional replenishment the PD rats and continuously well-fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as 'ATP/Pi ratio') in PD rats in contrast to an unchanged ATP/Pi ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 +/- 0.03 [SEM] vs 6.95 +/- 0.04; p less than 0.02). Tumor response in the PD group was significantly (p less than 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/Pi ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.
Sijens
P E
PE
Department of Radiotherapy, University Hospital Utrecht, The Netherlands.
van Echteld
C J
CJ
Neijt
J P
JP
Schipper
J
J
Dunki Jacobs
P B
PB
de Graaf
P W
PW
Seijkens
D
D
D000818:Animals; D003131:Combined Modality Therapy; D004035:Diet Therapy; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008727:Methotrexate / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D051381:Rats; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*
D004044:Dietary Proteins; D008727:Methotrexate