SENSITIZATION OF SKIN FIBROBLASTS TO UVA BY EXCESS IRON

Human skin chronically exposed to UV light is known to accumulate iron and to have an increased ferritin content as compared to unexposed ar eas. Iron accumulation is also found in many inflammatory skin disease s. Cultured human fibroblasts loaded with iron by incubation with non- toxic concentrations of the ferric nitrilotriacetate complex have been irradiated with low (up to 15 J/cm(2)) and moderate (up to 45 J/cm(2) ) UVA doses. At low irradiation doses, lipid peroxidation doubles with out affecting the viability of iron-loaded cells. At higher irradiatio n doses (30 J/cm(2)) the photocytotoxicity of UVA towards iron-loaded cells increases in a concentration-dependent manner with the iron load . Thus, after exposure to 30 J/cm(2) of UVA, the cytotoxicity is about 3-fold greater for cells incubated for 75 min with 100 mu M Of the fe rric complex as compared to those not treated with the ferric complex. Incubation with desferrioxamine, an extremely efficient chelator of f erric ion or vitamin E, a radical scavenger which blocks the lipid per oxidation radical chain, leads to marked inhibition of the sensitizing effects of iron on lipid peroxidation but is less effective for the s urvival of cells exposed to UVA. A similar concentration-dependent pro tective effect of desferrioxamine was observed with cultured fibroblas ts not treated with the ferric complex. It is suggested that the photo reduction of ferritin and/or other iron-containing proteins plays a si gnificant role in the UVA-induced photocytotoxicity of skin fibroblast s.