Ultraviolet light inactivation of zinc-mediated metallothionein induction in normal and repair-deficient human cells.

Synthesis of the low molecular weight, thiol-rich, metal-binding metallothioneins (MTS) is undetectable in normal human (NF) or xeroderma pigmentosum (XP) fibroblasts grown in the absence of excess ZnCl2. Addition of 200 microM ZnCl2 to the growth medium produces an increased MT synthesis rising from the basal rate to a rate at least 50-fold greater than basal rate within 7 h. MT induction kinetics in confluent and in exponentially growing subconfluent monolayers were indistinguishable. Zn2+-mediated MT induction is sensitive to actinomycin D suggesting that the induction process is under transcriptional control. Ultraviolet light irradiation causes a dose-dependent inactivation of Zn2+-mediated MT induction in both NF and XP cells. Post-irradiation incubation of UV-irradiated cells using liquid holding techniques leads to reactivation of Zn2+-mediated MT induction in NF cells but not in XP cells. These findings suggest the utility of MT induction produce transcription-terminating lesions, and (b) in evaluating cellular repair capacity for this class of DNA lesions.