Cadmium-induced inhibition of proliferation and differentiation of embryonal carcinoma cells and mechanistic aspects of protection by zinc.
Murine embryonal carcinoma cells have been used in in vitro models to study the effects of cadmium chloride on proliferation and differentiation of early embryonic cells. This approach allows the various cell types within the early embryo as well as several developmental mechanisms to be dissected and studied in isolation using larger numbers of cells than would be readily available from the embryo itself. The present study shows that both embryonal carcinoma cell proliferation and differentiation into parietal endoderm are inhibited by cadmium chloride. The effects are counteracted by the additional presence of zinc chloride. The uptake of cadmium into the cells is inhibited in the presence of zinc chloride, suggesting that competition between these metals for passage into the cells contributes to the mechanism underlying the protective effect of zinc. In addition, metallothionein gene expression is enhanced more rapidly after simultaneous incubation with zinc chloride, indicating that the attenuating effect of zinc on cadmium toxicity is also partly attributable to detoxification by metallothioneins.
Piersma
A H
AH
Unit Teratology, Endocrinology, and Perinatal Screening, National Institute of Public Health and Environmental Protection, The Netherlands.
Roelen
B
B
Roest
P
P
Haakmat-Hoesenie
A S
AS
van Achterberg
T A
TA
Mummery
C L
CL
D000818:Animals; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D018236:Carcinoma, Embryonal / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004707:Endoderm / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D007797:Laminin; D009363:Neoplasm Proteins; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc