Novel function of metallothionein in photoprotection: metallothionein-null mouse exhibits reduced tolerance against ultraviolet B injury in the skin.

We have shown previously that injection of cadmium chloride (Cd2+) depletes the number of ultraviolet B (UVB)-induced sunburn cells in the mouse skin in vivo, and that Cd2+ treatment enhances UVB resistance in cultured keratinocytes in vitro, indicating the photoprotective role of Cd2+-induced metallothioneins (MT) with antioxidant property against UVB injury; however, there has been no direct evidence for the role of MT in UV protection. To improve our understanding of MT in photoprotection, MT-null mouse deficient in its MT-1 and MT-2 genes was studied. Skin explants were preliminarily exposed to medium alone, Cd2+ and Cd2+ plus buthionine S,R-sulfoximine, an inhibitor of glutathione synthesis. We then compared the number of UVB-induced sunburn cells and apoptotic cells in the epidermis of MT-null mice with that of control mice using organ culture systems. The skin of MT-null mice developed a greater number of sunburn cells and apoptotic cells than did that of normal mice in all experimental conditions. These findings indicate that the skin of MT-null mouse is readily injured by UVB irradiation. MT-null mouse provided direct evidence of the photoprotective effect of cellular MT in the skin.