Ultraviolet radiation-induced metallothionein-I gene activation is associated with extensive DNA demethylation

Ultraviolet irradiation (UV) of cadmium-sensitive S49 mouse cells induces a large increase in cadmium-resistant variants. About 30%-40% of these variants make metallothionein (MT)-I mRNA while S49 cells do not. S49 cells contain two copies of the MT-I gene; both alleles are heavily methylated but can be conveniently distinguished by the methylation status of a single Hpa II site. In lines expressing MT-I, one allele becomes completely demethylated at all methylation-sensitive restriction sites examined over at least a 2.5 kb region spanning the MT-I gene. Activation of a quiescent gene by UV has implications for understanding the initiation of carcinogenesis.