Burns C P, Spector A A
Lipids. 1987 Mar;22(3):178-84. doi: 10.1007/BF02537299.
The fatty acid compositions of several tumors have been modified sufficiently to alter some of their properties and functions. These modifications were produced in culture by adding specific fatty acids to the growth medium or by feeding fat-supplemented diets to tumor-bearing mice. The phospholipid fatty acid composition of the plasma membrane was modified, but there were no changes in membrane phospholipid or cholesterol content or in phospholipid head group composition. Each of the most abundant membrane phosphoglyceride fractions exhibited some degree of fatty acid modification. Electron spin resonance measurements with nitroxystearate spin probes indicated that the fatty acid modifications were sufficient to alter the physical properties of the plasma membrane. The K'm for methotrexate uptake was reduced when the L1210 leukemia cells were enriched in linoleic acid. Even when the kinetics of uptake at 37 C were not altered, such as for melphalan and phenylalanine uptake, the temperature transition of transport was modified, indicating that these transport systems also are responsive to the membrane fatty acid modifications. Enrichment with highly polyunsaturated fatty acid did not affect either the growth rate or radiosensitivity of the L1210 leukemia. However, the sensitivity of the L1210 cells to the cytotoxic effects of Adriamycin and hyperthermia was increased. These findings suggest the possibility that fatty acid modification of tumors may be a useful adjunct to certain currently available therapeutic modalities.
几种肿瘤的脂肪酸组成已被充分改变，从而改变了它们的一些特性和功能。这些改变是在培养过程中通过向生长培养基中添加特定脂肪酸或给荷瘤小鼠喂食富含脂肪的饮食产生的。质膜的磷脂脂肪酸组成发生了改变，但膜磷脂或胆固醇含量以及磷脂头部基团组成没有变化。每种最丰富的膜磷酸甘油酯组分都表现出一定程度的脂肪酸改变。用硝基硬脂酸自旋探针进行的电子自旋共振测量表明，脂肪酸的改变足以改变质膜的物理性质。当L1210白血病细胞富含亚油酸时，甲氨蝶呤摄取的米氏常数降低。即使在37℃时摄取动力学没有改变，如美法仑和苯丙氨酸的摄取，转运的温度转变也发生了改变，这表明这些转运系统也对膜脂肪酸的改变有反应。富含高度多不饱和脂肪酸对L1210白血病的生长速率或放射敏感性均无影响。然而，L1210细胞对阿霉素和热疗细胞毒性作用的敏感性增加。这些发现提示肿瘤脂肪酸修饰可能是目前某些治疗方式的有用辅助手段。
