Difference in cadmium cytotoxicity in two kidney cell lines (LLC-PK(1) and MDCK) with special reference to metallothionein.

Proximal tubular dysfunction is a main toxic sign of chronic cadmium (Cd) poisoning, but it is not clear why the proximal tubular epithelium is more susceptible than distal tubular cells to Cd toxicity. Kidney cell lines of proximal (LLC-PK(1)) and distal (MDCK) tubular origins have been used to study comparative Cd toxicity. From cell morphology, cell numbers and cellular protein amounts, LLC-PK, cells were found to be more susceptible to Cd than MDCK cells. In LLC-PK(1) cells, cell number was decreased with time at concentrations of 25 mum Cd or more, whereas MDCK cells proliferated even under 50 mum Cd until hr 24. Cd accumulated in both cell types in a time- and dose-dependent manner; the accumulated Cd level was greater in LLC-PK(1) cells than in MDCK cells. The basal metallothionein (MT) amount was low and similar between the two cell lines; MT was induced in a dose- and time-dependent manner by Cd in MDCK cells whereas MT induction in LLC-PK(1) cells was observed only until Cd cytotoxicity overwhelmed cell viability. The vulnerability of LLC-PK(1) cells can be explained by the fact that they accumulate more Cd than MDCK cells, with insufficiently induced MT to sequester Cd ions.