Patients on peritoneal dialysis (PD) are exposed to peritoneal dialysis fluids with unphysiological properties. Local defense systems are of importance. In this respect, metallothionein (MT) might play an important role. Because nothing is known about the achievability of MT induction in peritoneum by zinc, we performed the following study. We investigated human peritoneal mesothelial cells (HPMC) from omentum and a mesothelioma cell (MTC) line after addition of zinc in concentrations from 35 to 350 microM. Measurements of MT-mRNA and protein (by immuncytochemistry [IHC], Western blots, and dot blots) were performed. Zinc caused a clear and highly significant fourfold increase of RNA in MTC and to a lower extent in HPMC (1.6-fold, P < 0.001). IHC demonstrated a clear induction in HPMC and MTC. Western and dot blots confirmed this and showed an increase of MT from 112-mg/g total protein (TP) to 410-mg/g TP. Zinc was able to upregulate MT significantly in HPMC and MTC on the RNA and protein level. Fourfold increases of MT were achievable.