Increased sensitivity to peroxidizing agents is correlated with an imbalance of antioxidants in normal melanocytes from melanoma patients.
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 polyunsaturated 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 microM 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 microM CUH and a cytotoxic effect at 20 microM. 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.
Grammatico
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Medical Genetic, University La Sapienza, Rome, Italy.
Maresca
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Roccella
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Roccella
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Biondo
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Catricalà
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Picardo
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D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001555:Benzene Derivatives / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008544:Melanocytes / Q000378:metabolism* / Q000648:ultrastructure; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D001555:Benzene Derivatives; D005231:Fatty Acids, Unsaturated; D016877:Oxidants; D014810:Vitamin E; D002374:Catalase; D013482:Superoxide Dismutase; C007164:cumene hydroperoxide