Simon L M, Robin E D, Theodore J
J Cell Physiol. 1981 Sep;108(3):393-400. doi: 10.1002/jcp.1041080313.
Metabolic studies in tumor cells have indicated that bioenergetic regulatory mechanisms geared to acute changes in oxygen availability are abnormal. In the present studies we have examined bioenergetic adaptations to chronic oxygen depletion in culture maintained tumor cells in comparison to normal cell lines. Activities of two key glycolytic enzymes (pyruvate kinase (PyKI) and phosphofructokinase (PFK)) were measured in two tumor cell lines (fibrosarcoma (FS) and Hela) and two normal cell lines (rat lung fibroblasts (RLF) and WI-38) maintained in culture for up to 96 hours under aerobic (PO2 approximately 140) and hypoxic PO2 approximately 15) conditions. Exposure to low O2 tensions for 96 hours resulted in significant increases in PyKi and PFK in both RLF and WI-38, ut did not alter activities of these enzymes in either FS or HeLa cell systems. Activities of two enzymes involved in O2 metabolism (cytochrome oxidase (CyOx) and superoxide dismutase (SOD) were also measured in the two tumor cell lines and in RLF. chronic hypoxia significantly decreased the activities of CyOx and SOD in RLF cell systems but did not alter the activities of these enzymes in the tumor cells. In these studies, the tumor-derived cell lines do not demonstrate specific enzymatic responses to sustained oxygen depletion in vitro noted in normal cell systems, suggesting significant abnormalities in regulatory mechanisms geared to chronic changes in molecular O2.
肿瘤细胞的代谢研究表明，针对氧供应急性变化的生物能量调节机制是异常的。在本研究中，我们检测了培养的肿瘤细胞与正常细胞系相比，对慢性缺氧的生物能量适应性。在有氧（PO₂约为140）和低氧（PO₂约为15）条件下，对两种肿瘤细胞系（纤维肉瘤（FS）和海拉细胞）和两种正常细胞系（大鼠肺成纤维细胞（RLF）和WI-38）进行长达96小时的培养，测量了两种关键糖酵解酶（丙酮酸激酶（PyKI）和磷酸果糖激酶（PFK））的活性。在RLF和WI-38中，暴露于低氧张力96小时导致PyKi和PFK显著增加，但在FS或海拉细胞系中这些酶的活性没有改变。还在两种肿瘤细胞系和RLF中测量了参与氧代谢的两种酶（细胞色素氧化酶（CyOx）和超氧化物歧化酶（SOD））的活性。慢性缺氧显著降低了RLF细胞系中CyOx和SOD的活性，但没有改变肿瘤细胞中这些酶的活性。在这些研究中，肿瘤衍生的细胞系在体外对持续缺氧没有表现出正常细胞系中所观察到的特异性酶反应，这表明针对分子氧慢性变化的调节机制存在显著异常。
