INCREASED SENSITIVITY TO PEROXIDATIVE AGENTS AS A POSSIBLE PATHOGENICFACTOR OF MELANOCYTE DAMAGE IN VITILIGO

To examine the sensitivity of vitiligo melanocytes to external oxidati ve stress, we studied enzymatic and non-enzymatic anti-oxidants in cul tured melanocytes of normal subjects (n = 20) and melanocytes from app arently normal skin of vitiligo patients (n = 10). The activity of sup eroxide dismutase and catalase and the intracellular concentrations of vitamin E and ubiquinone were evaluated in cultures at the fourth or fifth passage, In addition, cells were exposed to various concentratio ns of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66-20 mu M), for 1 and 24 h, Compared to normal melanocytes, vitiligo melanocytes s howed normal superoxide dismutase and significantly lower catalase act ivities and higher vitamin E and lower ubiquinone levels. At the conce ntration used, CUH did not significantly affect cell number or viabili ty of melanocytes after either period of culture, On the contrary, vit iligo melanocytes were susceptible to the toxic effect of CUH after 24 h of continuous treatment at concentrations greater than 6.6 mu M. Th e degree of CUH toxicity correlated strictly with the anti-oxidant pat tern, defined as the ratio between vitamin E concentration and catalas e activity, suggesting chat the alteration in the antioxidants was the basis for sensitivity to the external oxidative stress, Our results d emonstrate the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes and provide further support for a free radical-me diated damage as an initial pathogenic event in melanocyte degeneratio n in vitiligo.