Kirkpatrick John P, Brizel David M, Dewhirst Mark W
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Radiat Res. 2003 Mar;159(3):336-44. doi: 10.1667/0033-7587(2003)159[0336:ammoto]2.0.co;2.
Hypoxia imparts radioresistance to tumors, and various approaches have been developed to enhance oxygenation, thereby improving radiosensitivity. This study explores the influence of kinetic and physical factors on substrate metabolism in a tumor model, based on a Krogh cylinder. In tissue, aerobic metabolism is assumed to depend on glucose and oxygen, represented by the product of Michaelis-Menten expressions. For the base case, an inlet pO(2) of 40 mmHg, a hypoxic limit of 5 mmHg, and a tissue/capillary radius ratio of 10 are used. For purely aerobic metabolism, a hypoxic fraction of 0.16 and volume-average pO(2) of 8 mmHg are calculated. Reducing the maximum oxygen rate constant by 9%, decreasing the tissue cylinder radius by 5%, or increasing the capillary radius by 8% abolishes the hypoxic fraction. When a glycolytic term is added, concentration profiles are similar to the base case. Using a distribution of tissue/capillary radius ratios increases the hypoxic fraction and reduces sensitivity to the oxygen consumption rate, compared to the case with a single tissue/capillary radius ratio. This model demonstrates that hypoxia is quite sensitive to metabolic rate and geometric factors. It also predicts quantitatively the effects of inhibited oxygen metabolism and enhanced mass transfer on tumor oxygenation.
缺氧赋予肿瘤放射抗性，人们已开发出多种方法来增强氧合作用，从而提高放射敏感性。本研究基于克勒格圆柱模型，探讨动力学和物理因素对肿瘤模型中底物代谢的影响。在组织中，有氧代谢被认为取决于葡萄糖和氧气，由米氏方程的乘积表示。对于基础情况，使用入口pO₂为40 mmHg、缺氧极限为5 mmHg以及组织/毛细血管半径比为10。对于纯有氧代谢，计算出缺氧分数为0.16，体积平均pO₂为8 mmHg。将最大氧速率常数降低9%、将组织圆柱半径减小5%或使毛细血管半径增加8%可消除缺氧分数。当添加糖酵解项时，浓度分布与基础情况相似。与具有单一组织/毛细血管半径比的情况相比，使用组织/毛细血管半径比的分布会增加缺氧分数并降低对氧消耗率的敏感性。该模型表明缺氧对代谢率和几何因素相当敏感。它还定量预测了抑制氧代谢和增强传质对肿瘤氧合的影响。
