ISOLATION OF V79 FIBROBLAST CELL-LINES CONTAINING ELEVATED METALLOTHIONEIN LEVELS THAT HAVE INCREASED RESISTANCE TO THE CYTOTOXIC EFFECTS OF ULTRAVIOLET-A RADIATION

Isolated clones of V79 Chinese hamster lung fibroblasts, selected for resistance against cadmium toxicity, were exposed to monochromatic 365 nm ultraviolet-A (UVA; 320 nm to visible light) radiation and examine d for cell survival. All three of the Cd-resistant V79 clones (V79Cd) tested exhibited significant increases in survival after irradiation c ompared with control cultures similar to the increased survival observ ed in Zn acetate-induced V79 cells. Dose-modifying factors calculated for these survival experiments were all approximately 1.5. When charac terized for steady-state levels of metallothionein (MT) mRNA and assoc iated Cd-binding activity, all of the Cd-resistant V79Cd clones demons trated elevated constitutive levels of both, implicating MT as the mec hanism responsible for the observed cellular resistance to Cd and also to 365 nm WA radiation. However, whereas levels of intracellular MT p rotein correlated with differences in survival against Cd, MT intracel lular levels did not correlate well with protection against 365 nm UVA . Increased cell survival after exposure to 365 nm UVA radiation media ted by MT appeared to reach a threshold level and MT only provided a l imited degree of protection. Since UVA radiation is known to cause cel l death mediated through the intracellular generation of reactive oxyg en species (ROS), these results suggest that the role of MT in amelior ating cellular photooxidative damage produced by UVA is by reducing in tracellular ROS.