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+) dep letes the number of ultraviolet B (UVB)-induced sunburn cells in the m ouse skin in vivo, and that Cd2+ treatment enhances UVB resistance in cultured keratinocytes in vitro, indicating the photoprotective role o f Cd2+-induced metallothioneins (MT) with antioxidant property against WB injury; however, there has been no direct evidence for the role of MT in UV protection. To improve our understanding of MT in photoprote ction, MT-null mouse deficient in its MT-1 and MT-2 genes was studied. Skin explants were preliminarily exposed to medium alone, Cd2+ and Cd 2+ plus buthionine S,R-sulfoximine, an inhibitor of glutathione synthe sis. We then compared the number of UVB-induced sunburn cells and apop totic 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 gre ater number of sunburn cells and apoptotic cells than did that of norm al mice in all experimental conditions. These findings indicate that t he skin of MT-null mouse is readily injured by WE irradiation. MT-null mouse provided direct evidence of the photoprotective effect of cellu lar MT in the skin.