INVIVO METABOLIC EFFECTS OF HYPERGLYCEMIA IN MURINE RADIATION-INDUCED FIBRO-SARCOMA - A P-31 NMR INVESTIGATION
INVIVO METABOLIC EFFECTS OF HYPERGLYCEMIA IN MURINE RADIATION-INDUCED FIBRO-SARCOMA - A P-31 NMR INVESTIGATION
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DOI：
10.1073/pnas.81.20.6496
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
ACKERMAN, JJH
中科院分区：
文献类型：
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作者：
EVELHOCH, JL;SAPARETO, SA;ACKERMAN, JJH
高血糖诱导的体内代谢变化在s.c.用31 P表面螺旋NMR检查在雌性C3 H/Anf小鼠上生长的鼠RIF-1肿瘤。通过腹膜内推注0.3 ml 50%葡萄糖水溶液，血清葡萄糖水平升高4倍。根据Pi的化学位移计算肿瘤pH值，并通过峰面积的Erbsson规则积分确定相对磷酸肌酸和ATP浓度。肿瘤pH在2小时内降低0.45 U，而磷酸肌酸浓度降低约0.45 U。50%（n = 9）。初始肿瘤pH与Pi：ATP 2的初始峰强度比呈负相关（r = -0.77）。在大量肿瘤（n = 4）中，观察到2个pH群体。在这些肿瘤中，一个群体不受高血糖症的影响，另一个显示pH值下降。在其他肿瘤（n = 5）中，pH值分布随着pH值下降而变宽。在这些肿瘤中，观察到的磷酸肌酸浓度降低与根据测量的肿瘤pH值对细胞内肌酸激酶平衡的影响计算的结果相关（n = 18，r = 0.91）。肿瘤中Pi分布的这种相关性和考虑表明，对于RIF-1肿瘤，通过31 P NMR测量的pH值受到细胞内pH值的严重影响。存在2个不同的肿瘤pH群体或pH分布变宽可能反映了肿瘤微细胞结构的变化。对照实验显示，在腹膜内推注0.3 ml等渗盐水后，肿瘤pH值和高能磷酸盐浓度的变化可忽略不计。向有或无肿瘤的小鼠注射葡萄糖后，观察到腿部肌肉pH值和高能磷酸盐浓度的变化可以忽略不计。显然，通过腹膜内葡萄糖注射诱导的高血糖症有效降低鼠RIF-1肿瘤的肿瘤pH。
The hyperglycemia-induced in vivo metabolic changes produced in s.c. murine RIF-1 tumors, grown on female C3H/Anf mice, were examined with 31P surface-coil NMR. Serum glucose levels were elevated 4-fold by bolus i.p. injection of 0.3 ml of an aqueous 50% glucose solution. Tumor pH was calculated from the chemical shift of Pi and relative phosphocreatine and ATP concentrations were determined by Simpson''s rule integration of the peak areas. Tumor pH decreased by 0.45 U over 2 h while phosphocreatine concentrations decreased by .apprx. 50% over the same time period (n = 9). Initial tumor pH correlated inversely with the initial peak intensity ratio of Pi:ATP2 (r = -0.77). In a significant number of tumors (n = 4), 2 pH populations were observed. In these tumors, one population was unaffected by hyperglycemia and the other showed a decrease in pH. In the other tumors (n = 5), the pH distribution broadened as the pH decreased. In these tumors, the observed decrease in phosphocreatine concentration correlated with that calculated from the effect of measured tumor pH on the intracellular creatine kinase equilibrium (n = 18, r = 0.91). This correlation and consideration of the Pi distribution in the tumor suggest that the pH measured by 31P NMR is weighted heavily by intracellular pH for the RIF-1 tumor. The presence of 2 distinct tumor pH populations or a broadened pH distribution likely reflects variations in tumor microcellular environmment. Control experiments showed negligible changes in tumor pH and high energy phosphate concentrations after bolus i.p. injection of 0.3 ml of isotonic saline. Negligible changes in leg muscle pH and high energy phosphate concentrations were observed after glucose injection into mice with or without tumors. Apparently hyperglycemia induced by i.p. glucose injection is effective in lowering the tumor pH of the murine RIF-1 tumor.