Modification by Tissue Glutathione Levels Noninvasive Imaging of Tumor Redox Status and Its Updated Version
Modification by Tissue Glutathione Levels Noninvasive Imaging of Tumor Redox Status and Its Updated Version
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发表时间：
2001
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通讯作者：
P. Kuppusamy;G. Ilangovan;A. Cardounel;J. Zweier;Ken‐ichi Yamada;M. Krishna;James B. Mitchell
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作者：
P. Kuppusamy;G. Ilangovan;A. Cardounel;J. Zweier;Ken‐ichi Yamada;M. Krishna;James B. Mitchell
诸如放射或化学疗法的治疗方案试图利用正常组织和恶性组织之间的生理差异。组织氧化还原状态和pO 2是假设在正常和恶性组织中不同的两个因素。可以检测上述生理参数的细微差异的方法将极大地有助于设计适当的治疗策略。我们先前已经使用体内电子顺磁共振（EPR）光谱和成像技术，并且显示与正常组织相比，肿瘤组织是高度还原和缺氧的（P. Kuppusamy等人，癌症研究所，58：1562-1568，1998）。本研究的目的是获得空间分辨的氧化还原数据，从正常和肿瘤组织的辐射诱导的纤维肉瘤（RIF-1）荷瘤小鼠，并检查细胞内谷胱甘肽（GSH）的作用，对组织的氧化还原状态。使用低频（1.3 GHz）在体内EPR光谱和成像技术与氮氧氧化还原探针进行实验。GSH合成抑制剂L-丁硫氨酸-S，R亚砜亚胺（BSO）用于消耗组织GSH水平。结果表明，与正常组织相比，肿瘤组织中存在显着的氧化还原状态的异质性。与荷瘤小鼠的正常组织相比，肿瘤组织显示至少4倍的GSH水平。BSO治疗也显示了肿瘤组织中GSH的差异性耗竭和还原当量。因此，似乎存在肿瘤氧化还原状态的显著异质性，并且肿瘤氧化还原状态的操纵在肿瘤生长和治疗中可能是重要的。
Therapeutic regimens such as radiation or chemotherapy attempt to exploit the physiological differences between normal and malignant tissue. Tissue redox status and pO2 are two factors that are hypothesized to be different in normal and malignant tissues. Methods that can detect subtle differences in the above physiological parameters would greatly aid in devising appropriate treatment strategies. We have previously used in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques and shown that tumor tissues are highly reducing and hypoxic compared with normal tissues (P. Kuppusamy et al., Cancer Res., 58: 1562–1568, 1998). The purpose of the present study was to obtain spatially resolved redox data from normal and tumor tissues of radiation-induced fibrosarcoma (RIF-1) tumor-bearing mice and to examine the role of intracellular glutathione (GSH) on the tissue redox status. Experiments were performed using low-frequency (1.3 GHz) in vivo EPR spectroscopy and imaging techniques with a nitroxide redox probe. L-buthionine-S,Rsulfoximine (BSO), an inhibitor of GSH synthesis, was used to deplete tissue GSH levels. The results show the existence of significant heterogeneity of redox status in the tumor tissue compared with normal tissue. The tumor tissues show at least 4-fold higher concentrations of GSH levels compared with normal tissues in the tumor-bearing mice. Also BSO treatment showed a differential depletion of GSH and reducing equivalents in the tumor tissue. Thus, it appears that there is significant heterogeneity of tumor redox status and that manipulation of the tumor redox status may be important in tumor growth and therapy.