POSSIBLE ROLE OF METALLOTHIONEIN IN THE CELLULAR DEFENSE-MECHANISM AGAINST UVB IRRADIATION IN NEONATAL HUMAN SKIN FIBROBLASTS

The role of metallothionein (MT) in protecting skin cells against UVB irradiation was investigated. Fibroblast strains from normal adult (HS -K) and neonatal(NB1RGB) human skins as well as keratinocyte strains f rom human skin (SV40-HSK) and newborn Balb/c mouse skin (Pam 212) were exposed to UVB irradiation. The sensitivity of HS-K and NB1RGB cells to UVB irradiation was similar; those of SV40-HSK and Pam 212 cells we re two- and six-fold as sensitive to UVB irradiation as HS-K cells, re spectively. The HS-K cells contained the greatest cellular reduced for m of glutathione (GSH) levels compared to the three other skin cells: the levels were 13-, 7- and 6-fold of those in NB1RGB, SV40-HSK and Pa m 212 cells, respectively. These results indicated that the sensitivit y of skin cells to UVB irradiation was not always associated with thei r endogenous GSH levels. In particular, despite the fact that NB1RGB c ells contained a relatively small amount of GSH, they were less sensit ive to UVB irradiation. NBIRGB cells contained 4-30 times more MT than those in other skin cells examined. The sulfhydryl residues of MT mol ecules in the NBIRGB cells were estimated to be mostly unoccupied by m etals, suggesting they act in a similar way to those of GSH. Moreover, NB1RGB cells in which the MT content was elevated by dexamethasone (1 mu M) or Zn2+ (7 mu g/mL) treatment were more resistant to UVB irradi ation than nontreated ones. These results suggest that, at least in ne onatal human skin fibroblasts, MT may play a role in protection agains t UVB irradiation.