Increased sensitivity to peroxidizing agents is correlated with an imbalance of antioxidants in normal melanocytes from melanoma patients
Increased sensitivity to peroxidizing agents is correlated with an imbalance of antioxidants in normal melanocytes from melanoma patients
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DOI：
10.1111/j.1600-0625.1998.tb00325.x
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发表时间：
1998-08-01
影响因子：
3.6
通讯作者：
Picardo, M
中科院分区：
文献类型：
--
作者：
Grammatico, P;Maresca, V;Picardo, M
我们之前已经证明，黑色素瘤患者的一些正常黑色素细胞培养物中抗氧化系统存在不平衡。为了评估抗氧化剂的改变是否可能是对过氧化剂暴露敏感性增加的基础，在正常个体（n = 11）和黑色素瘤患者（n = 11）的培养黑素细胞中，通过分光光度计评估超氧化物歧化酶和过氧化氢酶活性，并通过气相色谱质谱法测定维生素E和细胞膜多不饱和脂肪酸的水平。在 11 个黑色素瘤患者黑色素细胞培养物中，有 5 个与正常个体相比，发现与维生素 E (Vit E) 浓度增加相关的过氧化氢酶活性 (Cat) 显着降低，但未观察到超氧化物歧化酶活性 (SOD) 的显着改变。在细胞膜的多不饱和脂肪酸的百分比中检测到了广泛的变异性，并且在 SOD/Cat 比率和亚油酸的百分比之间发现了相关性，表明酶抗氧化剂的不平衡导致了脂质过氧化过程。这些培养物的电子显微镜检查显示质膜和核折叠以及细胞质光液泡中有许多微绒毛。此外，一些细胞含有几个圆形致密体和许多球形片层，可能代表未成熟的黑素体。用0.66至20μM的氢过氧化异丙苯处理不会对正常个体的黑素细胞的细胞活力产生显着的改变。相反，在黑色素瘤患者的黑色素细胞中，与 Vit E/Cat 的比率（被认为是抗氧化剂失衡的参数）相关，在 0.66 μM CUH 时观察到刺激作用，在 20 μM CUH 时观察到细胞毒性作用。 总之，我们的结果表明，黑色素瘤患者的正常黑色素细胞中可能存在清除剂系统的结构性改变，这可能是对促氧化剂敏感性增加的基础。
We have previously shown an imbalance of the antioxidant system in some cultures of normal melanocytes from patients with melanoma. In order to evaluate if the alteration of the antioxidants could be the basis of an increased sensitivity to exposure to peroxidative agents, in cultured melanocytes from normal individuals (n = 11) and from patients with melanoma (n = 11), superoxide dismutase and catalase activities were evaluated by spectrophotometer, and the levels of vitamin E and of the polyunsaturated fatty acid of cell membranes were determined by gas chromatography mass spectrometry. In 5 out of the 11 cultures of melanocytes from melanoma patients, with respect to those from normal individuals, a significant decrease of catalase activity (Cat) associated with an increase of vitamin E (Vit E) concentration was found, whereas no significant modification of superoxide dismutase activity (SOD) was observed. A wide range of variability was detected in the percentage of the poly-unsaturated fatty acids of the cell membranes and a correlation was found between the ratio SOD/Cat and the percentage of linoleic acid, indicating that the imbalance of the enzymatic antioxidants leads to a lipoperoxidative process. The electron microscopic examination of these cultures revealed many microvilli in the plasma membranes and nuclear infoldings and in the cytoplasm light vacuoles. Moreover some cells contained several dense bodies with a round shape and numerous spherical lamellae possibly representing immature melanosomes. Treatment with cumene hydroperoxide between 0.66 and 20 mu M did not produce a significant modification of cell viability in melanocytes from normal individuals. On the contrary in melanocytes from melanoma patients correlated with the ratio Vit E/Cat, considered as a parameter of the antioxidant imbalance, a stimulatory effect was observed at 0.66 mu M CUH and a cytotoxic effect at 20 mu M. In conclusion our results suggest that a constitutional alteration of the scavenger system could be present in normal melanocytes from melanoma patients and that this could be the basis for an increased sensitivity to pro-oxidant agents.