Reduced uptake and enhanced release of cadmium in cadmium-resistant metallothionein null fibroblasts

Metallothionein (MT) is known to play a predominant role in the protection of cells from cadmium (Cd) toxicity. To investigate other factors involved in Cd resistance, we established Cd-resistant cell lines from simian virus 40-transformed MT null fibroblasts. Cd-resistant MT null cells, Cd-rA7 and Cd-rB5, developed approximately 10-fold resistance to Cd compared to parent al cells, but showed no cross-resistance to Zn, Cu, Hg, Ni, As, cisplatin o r H2O2. Accumulation of Cd in the resistant cells was 13-18% of that of par ental cells after treatment with Cd for 24 h. A short-term experiment revea led that the rate of Cd incorporation into the Cd-resistant cells was suppr essed, and the rate of Cd release was enhanced in the resistant cells compa red with that of parental cells. These results indicate that the altered tr ansport of Cd, slow uptake and rapid release, may confer resistance to Cd o n the Cd-resistant cells established from MT null fibroblasts. (C) 1999 Els evier Science Inc.