Khan S H, Emerit I
J Free Radic Biol Med. 1985;1(5-6):443-9. doi: 10.1016/0748-5514(85)90159-x.
The chromosome-damaging effect of PMA in blood cultures is mediated by secondary products which are formed by the cells in response to the interaction with this tumor promoter. Since this effect could be influenced by antioxidant enzymes and by inhibitors of arachidonic acid metabolism, the present study was undertaken in order to determine whether the formation of these clastogenic substances is concomitant with the formation of AA metabolites and other lipid peroxidation products. Besides the clastogenic effect of ethyl-acetate extracts, the similarities of cytogenetic and biochemical results (conjugated dienes and TBA-reactive material) obtained for the influence of other blood cells than lymphocytes in the culture system, the importance of PHA stimulation and the protective effect of antioxidant enzymes were arguments in favour of a causal relationship between chromosome damage and lipid peroxidation (enzymatic or nonenzymatic). If AA release from membrane phospholipids was prevented by inhibition of phospholipase A2, neither conjugated dienes nor TBA-reactive material were found, and chromosome damage was reduced considerably. However, the results obtained with inhibitors of the cyclo- and lipoxygenase pathway were not conclusive, and discrepancies were also observed in the time course of appearance of clastogenic material and lipid peroxidation products.
佛波酯（PMA）在血培养中对染色体的损伤作用是由次级产物介导的，这些次级产物是细胞在与这种肿瘤启动子相互作用时形成的。由于这种效应可能受抗氧化酶和花生四烯酸代谢抑制剂的影响，因此进行了本研究，以确定这些致断裂物质的形成是否与花生四烯酸（AA）代谢产物及其他脂质过氧化产物的形成同时发生。除了乙酸乙酯提取物的致断裂作用外，对于培养系统中淋巴细胞以外的其他血细胞的影响所获得的细胞遗传学和生化结果（共轭二烯和硫代巴比妥酸反应性物质）的相似性、PHA刺激的重要性以及抗氧化酶的保护作用，都支持染色体损伤与脂质过氧化（酶促或非酶促）之间存在因果关系这一观点。如果通过抑制磷脂酶A2来阻止膜磷脂释放AA，则既未发现共轭二烯也未发现硫代巴比妥酸反应性物质，并且染色体损伤显著减少。然而，用环氧化酶和脂氧合酶途径抑制剂获得的结果并不确凿，并且在致断裂物质和脂质过氧化产物出现的时间进程中也观察到了差异。
