Schwartsburd P M, Lankin V Z
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Puschino, Moscow Region.
Med Oncol. 1994;11(3-4):101-10. doi: 10.1007/BF02999857.
We examined the role of main cell protective mechanisms in retaining the high resistance of ascitic cells (EAC, ZAH) to lipid peroxidation with respect to different stages of tumor-organism metabolic interactions. The following mechanisms were studied: (1) the activity of main EAC enzymatic antioxidants (GSH-Px, SOD); (2) changes in lipid metabolism, especially the content of the main PUFA (linoleic and arachidonic fatty acids) in EAC cells; (3) comparison of intracellular resistance between EAC/ZAH cytoplasmic sections (containing LP-granules or not) to lipid peroxidation (initialized directly by UV-light). We found that the high resistance to lipid peroxidation was typical for cytoplasma sections (without LP-granules) on all stages of tumor development in vivo. The intracellular LP-granules become the main sensitive targets for FR-action, but only in the chronic hypoxia state of EAC/ZAH tumor cells. The latter effect developed in close correlation with the following metabolic interactions: (1) increasing the proportion of PUFA (especially, arachidonic and linoleic acids) transported to EAC tumor cells from host organs and accumulated mainly in tumor LP-granules, and (2) decreasing the alpha-tocopherol content of these hypoxic EAC cells while no activation of the main cell antioxidative enzymes (GSH-Px, SOD) took place. The vitality and high resistance of EAC stationary cells were accompanied by the 'paradoxical' state with great differences between the resistance of the intracellular PUFA-rich granules and other cytoplasmic sections. A similar state was found in stationary ZAH cells. The cell state is in good agreement with the Dormandy's suggestion that PUFA-rich granules can trap reactive radical species preventing their interaction with 'critical' PUFA-membranes.
我们研究了主要细胞保护机制在腹水细胞（EAC、ZAH）对脂质过氧化保持高抗性方面的作用，该作用与肿瘤 - 机体代谢相互作用的不同阶段有关。研究了以下机制：（1）EAC主要酶促抗氧化剂（谷胱甘肽过氧化物酶、超氧化物歧化酶）的活性；（2）脂质代谢的变化，特别是EAC细胞中主要多不饱和脂肪酸（亚油酸和花生四烯酸）的含量；（3）比较EAC/ZAH细胞质部分（含或不含LP颗粒）对脂质过氧化（直接由紫外线引发）的细胞内抗性。我们发现，在体内肿瘤发展的所有阶段，细胞质部分（无LP颗粒）对脂质过氧化具有高抗性是典型特征。细胞内LP颗粒成为自由基作用的主要敏感靶点，但仅在EAC/ZAH肿瘤细胞的慢性缺氧状态下如此。后一种效应与以下代谢相互作用密切相关：（1）从宿主器官转运至EAC肿瘤细胞并主要积聚在肿瘤LP颗粒中的多不饱和脂肪酸（尤其是花生四烯酸和亚油酸）比例增加，以及（2）这些缺氧EAC细胞的α - 生育酚含量降低，同时主要细胞抗氧化酶（谷胱甘肽过氧化物酶、超氧化物歧化酶）未被激活。EAC静止细胞的活力和高抗性伴随着一种“矛盾”状态，即富含多不饱和脂肪酸的颗粒与其他细胞质部分的抗性存在巨大差异。在静止的ZAH细胞中也发现了类似状态。这种细胞状态与多尔曼迪的观点一致，即富含多不饱和脂肪酸的颗粒可以捕获活性自由基，防止它们与“关键”的多不饱和脂肪酸膜相互作用。
