METABOLIC RESPONSE OF AH13R RAT-TUMORS TO CYCLOPHOSPHAMIDE AS MONITORED BY PO2 AND PH SEMIMICROELECTRODES
METABOLIC RESPONSE OF AH13R RAT-TUMORS TO CYCLOPHOSPHAMIDE AS MONITORED BY PO2 AND PH SEMIMICROELECTRODES
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DOI：
10.1016/0959-8049(93)90587-6
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发表时间：
1993-01-01
影响因子：
8.4
通讯作者：
RAJEWSKY, MF
中科院分区：
文献类型：
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作者：
JAHDE, E;ROSZINSKI, S;RAJEWSKY, MF
微环境的组成对细胞对细胞毒性药物的反应有重要影响。利用pH和pO2半微电极，我们监测了AH13r大鼠肿瘤在化疗后随时间的代谢变化。在治疗前，肿瘤包含大面积缺氧（平均pO2类似于4 mmHg），其特征是酸性代谢物明显积聚（平均pH值为6.65）。给药环磷酰胺（40 mg/kg体重）使肿瘤缩小到预处理体积的15%，生长延迟12天。随着体积的缩小，肿瘤变得再氧化（平均pO2类似于7 mmHg），在2-4天内达到最大值，同时pH值向更碱性的值转移（平均0.17 U）。这些变化与次全坏死的发展相一致。在肿瘤再生早期，pH和pO2直方图恢复到控制值。这些数据证实并扩展了先前的研究结果，在这些研究中，非侵入性技术已被应用于监测体内恶性肿瘤治疗诱导的代谢变化。此外，这些结果支持这样一种观点，即考虑到先前治疗过程引起的生理变化，选择和安排治疗药物可能会提高抗癌治疗的有效性。
The composition of the microenvironment has an important influence on the cellular response to cytotoxic agents. Using pH and pO2 semi-microelectrodes, we have monitored metabolic changes in AH13r rat tumours as a function of time after subcurative chemotherapy. Prior to therapy, tumours contained large areas considered hypoxic (mean pO2 is similar to 4 mmHg) and are characterised by a marked accumulation of acidic metabolites (mean pH 6.65). Administration of cyclophosphamide (40 mg/kg body weight) resulted in tumour regression to 15% of pretreatment volumes and a growth delay of 12 days. Concomitant with volume reduction, tumours became reoxygenated (mean pO2 is similar to 7 mmHg), with maximum values being reached within 2-4 days, paralleled by a shift of pH to more alkaline values (0.17 U on average). These changes coincided with the development of subtotal necrosis. During early tumour regrowth, the pH and pO2 histograms returned to control values. These data corroborate and extend the results of previous studies in which noninvasive techniques had been applied for the monitoring of treatment-induced metabolic changes in malignant tumours in vivo. In addition, these results support the notion that the effectiveness of anticancer therapy might be improved by selecting and scheduling therapeutic agents in consideration of physiological changes caused by preceding courses of treatment.