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 som e 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 cul tured melanocytes from normal individuals (n = 11) and from patients w ith melanoma (n = 11), superoxide dismutase and catalase activities we re evaluated by spectrophotometer, and the levels of vitamin E and of the polyunsaturated fatty acid of cell membranes were determined by ga s chromatography mass spectrometry. In 5 out of the 11 cultures of mel anocytes from melanoma patients, with respect to those from normal ind ividuals, a significant decrease of catalase activity (Cat) associated with an increase of vitamin E (Vit E) concentration was found, wherea s no significant modification of superoxide dismutase activity (SOD) w as observed. A wide range of variability was detected in the percentag e of the poly-unsaturated fatty acids of the cell membranes and a corr elation was found between the ratio SOD/Cat and the percentage of lino leic acid, indicating that the imbalance of the enzymatic antioxidants leads to a lipoperoxidative process. The electron microscopic examina tion of these cultures revealed many microvilli in the plasma membrane s and nuclear infoldings and in the cytoplasm light vacuoles. Moreover some cells contained several dense bodies with a round shape and nume rous spherical lamellae possibly representing immature melanosomes. Tr eatment with cumene hydroperoxide between 0.66 and 20 mu M did not pro duce a significant modification of cell viability in melanocytes from normal individuals. On the contrary in melanocytes from melanoma patie nts correlated with the ratio Vit E/Cat, considered as a parameter of the antioxidant imbalance, a stimulatory effect was observed at 0.66 m u M CUH and a cytotoxic effect at 20 mu M. In conclusion our results s uggest 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.