Sijens P E, van Echteld C J, Neijt J P, Schipper J, Dunki Jacobs P B, de Graaf P W, Seijkens D
Department of Radiotherapy, University Hospital Utrecht, The Netherlands.
NMR Biomed. 1989 Jun;2(1):12-8. doi: 10.1002/nbm.1940020104.
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.
通过体内31P核磁共振波谱法研究了营养调控及随后的化疗对移植大鼠横纹肌肉瘤生长和代谢的影响。营养调控通过给予不含蛋白质且含75.5%葡萄糖的蛋白质缺乏饮食来实现。5天后，给蛋白质缺乏的大鼠（PD大鼠）补充含27%蛋白质和47.3%葡萄糖的正常蛋白质饮食。营养补充24小时后，PD大鼠和持续喂养良好的对照组（NP大鼠）接受甲氨蝶呤（MTX，30mg/kg，腹腔注射）。MTX给药24小时后对肿瘤进行31P核磁共振波谱分析，结果显示PD大鼠中核苷三磷酸与无机磷酸盐的比率（称为“ATP/Pi比率”）降低，而NP对照组的ATP/Pi比率未变。在给予MTX时，PD大鼠的肿瘤pH值显著低于NP组（6.75±0.03[标准误]对6.95±0.04；p<0.02）。与NP组相比，PD组的肿瘤反应显著增强（p<0.01）。这些发现表明，一段时间的饮食蛋白质缺乏与高糖负荷相结合，随后进行营养补充会损害肿瘤代谢。代谢状态的改变表现为肿瘤酸化以及ATP/Pi比率的明显变化，并且似乎与对MTX化疗的易感性增强有关。
