Galeotti T, Borrello S, Minotti G, Masotti L
Ann N Y Acad Sci. 1986;488:468-80. doi: 10.1111/j.1749-6632.1986.tb46579.x.
Membranes isolated from tumor cells present profound alterations in their composition, structural organization, and functional properties. In this study we have reported some of these alterations in microsomal and plasma membranes of hepatomas with different growth rate and degree of differentiation. The chemical parameters studied were the phospholipid-to-protein, the cholesterol-to-protein, and the cholesterol-to-phospholipid ratios and the fatty acid composition of the phospholipids. The physical parameters were the molecular order (static) and the fluidity (dynamic), determined, respectively, as the order parameter [P2] and the correlation time tau R of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). The functional property investigated was the ability of the membranes to undergo superoxide-induced lipid peroxidation, determined as byproduct (malondialdehyde and lipid hydroperoxides) formation and as changes in the fatty acid acyl residues. Changes in the physical state of the membrane, induced by oxy radicals, were also monitored during lipid peroxidation. A study of the antioxidant activity of the tumor cell, in terms of oxy radical enzymatic defenses (superoxide dismutase, glutathione peroxidase and catalase) was also performed. The main results obtained are the following: hepatoma membranes possess a lower phospholipid content and a lower degree of fatty acid unsaturation; on the other hand, the cholesterol-to-phospholipid ratio is increased; the physical state appears characterized by an increased rigidity (increased molecular order of the lipids and decreased fluidity); the membrane peroxidizability is markedly depressed and its order parameter, in contrast to liver membranes, does not increase with exposure to the action of O2- radicals; and the oxy radical enzymatic defense mechanisms are decreased. All these alterations increase with increasing growth rate and dedifferentiation of the tumor. Considering all of the data, we are inclined to think that tumor membranes are altered structurally and functionally in part as the result of an oxy radical-induced damage that takes place in vivo under conditions of increased oxygen toxicity.
从肿瘤细胞分离出的膜在其组成、结构组织和功能特性方面呈现出深刻的改变。在本研究中，我们报告了不同生长速率和分化程度的肝癌微粒体膜和质膜中的一些此类改变。所研究的化学参数为磷脂与蛋白质的比例、胆固醇与蛋白质的比例、胆固醇与磷脂的比例以及磷脂的脂肪酸组成。物理参数为分子有序性（静态）和流动性（动态），分别通过荧光探针1,6 - 二苯基 - 1,3,5 - 己三烯（DPH）的有序参数[P2]和相关时间τR来确定。所研究的功能特性是膜发生超氧化物诱导的脂质过氧化的能力，通过副产物（丙二醛和脂质氢过氧化物）的形成以及脂肪酸酰基残基的变化来确定。在脂质过氧化过程中，还监测了由氧自由基诱导的膜物理状态的变化。还对肿瘤细胞的抗氧化活性进行了研究，涉及氧自由基酶防御（超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶）。获得的主要结果如下：肝癌膜的磷脂含量较低，脂肪酸不饱和度较低；另一方面，胆固醇与磷脂的比例增加；物理状态表现为刚性增加（脂质的分子有序性增加，流动性降低）；膜的过氧化能力明显降低，并且与肝细胞膜相比，其有序参数不会随着暴露于O2-自由基的作用而增加；氧自由基酶防御机制降低。所有这些改变随着肿瘤生长速率和去分化程度的增加而增加。综合所有数据，我们倾向于认为肿瘤膜在结构和功能上的改变部分是由于在体内氧毒性增加的条件下发生的氧自由基诱导的损伤所致。
