THIOLS AND SELENIUM - PROTECTIVE EFFECT ON HUMAN SKIN FIBROBLASTS EXPOSED TO UVA RADIATION

The sensitivity of human dermal fibroblasts to WA radiation has been l inked to a decrease in intracellular glutathione (GSH) levels. GSH (ga mma-glutamyl-cystemyl-glycine) is a radical scavenger and a cofactor f or protective enzymes such as selenium-dependent GSH peroxidases. In t his study, we examine the possibility of a cooperative interaction bet ween three cysteine delivery systems and selenium in protecting human cultured fibroblasts exposed to WA radiation. Cells were irradiated (9 , 15 and 20 J cm(-2)) following incubation with N-acetyl-cysteine (NAG , 5 mM), N-acetyl-homocysteine-thiolactone (citiolone (CTT),1 mM) or L -2-oxothiazolidine-4-carboxylate (OTC, 1 mM), The modulation of the in tracellular GSH levels by the addition of the different compounds was determined by enzymatic and separative methods. Cells were harvested f or survival analysis by measuring the ability of the cell to adhere an d proliferate. Treatments with NAC and CIT resulted in a significant r ise in GSH levels compared with control cells, with protection against WA radiation. OTC did not induce any rise in GSH level; nevertheless, the protective effect afforded by OTC is similar to that observed wit h NAC and CIT. Moreover, selenium (0.1 mg l(-1)), as sodium selenite, significantly increased the protective efficiency of NAC and CIT, but not of OTC. Although the precise mechanism is not known, thiol molecul es can inhibit the deleterious effects of UVA radiation. These results provide evidence that compounds capable of inducing GSH synthesis can act with selenium to protect cells against UVA damage. (C) 1997 Elsev ier Science S.A.