Application of metallothionein null cells to investigation of cadmium transport.
Metallothionein (MT) is an important factor for cadmium resistance in mammalian cells. Most Cd-resistant cell lines thus far established have shown enhanced production of MT protein. However, the presence of high concentrations of MT, which traps cellular cadmium ions efficiently, has hindered the investigation of cadmium transport in Cd-resistant cells. Utilization of MT null mice or cultured cells derived from MT null mice is a useful way to isolate and characterize non-MT factor(s) for Cd resistance. Primary cultured cells derived from embryos of MT-I/II null mouse showed an increased sensitivity to cadmium compared with control cells. Immortalization of these cells by introducing simian virus 40 large T antigen cDNA has enabled the development of Cd-resistant MT null cells. The established Cd-resistant MT null cells exhibited a reduced accumulation of cadmium due to a decreased rate of cellular cadmium uptake. Application of the multitracer technique has demonstrated that the uptake of Mn(II) was also markedly reduced in Cd-resistant MT null cells. Kinetic and competition studies on Cd(II) and Mn(II) uptake in these cells revealed that a high-affinity transport system for Mn(II) is used, at least in part, for cellular Cd(II) uptake. Thus, the utilization of MT null cells has permitted the detection of a novel cadmium transport system.
Himeno
Seiichiro
S
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo108-8641, Japan. himenos@pharm.kitasato-u.ac.jp
D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000378:metabolism*; D002461:Cell Line, Transformed; D008345:Manganese / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D002104:Cadmium; D008345:Manganese; D008668:Metallothionein