Mechanisms of cadmium toxicity in terrestrial pulmonates: programmed cell death and metallothionein overload.
A sublethal dose of cadmium (Cd2+) administered via the diet during short-term exposure over 10 d induced programmed cell death in the hepatopancreas of the terrestrial pulmonate snail Helix pomatia. Condensed cell residues were predominantly phagocytosed by calcium cells, suggesting a specific function of these epithelial cells in metal detoxification or in clearing the organ of cellular debris from cell death. The considerable cell loss recorded by histological analysis was accompanied by enhanced cell proliferation. Intoxication with Cd was further associated with the pronounced abundance of residual bodies, predominantly recorded in excretory cells, and with pathological changes in the endoplasmic reticulum. During long-term Cd exposure, mortality increased with increasing Cd concentrations in the diet, as demonstrated by feeding experiments in the laboratory. Lethal effects of Cd appeared to be correlated with Cd overloading of the Cd-specific metallothionein isoform (Cd-MT), isolated and characterized previously from the animal's hepatopancreas. Stoichiometric analysis shows that the capacity of Cd-MT to bind six molar equivalents of Cd corresponds to a tissue Cd concentration of approximately 4 micromol/g dry weight. At this tissue concentration, all high-affinity metal-binding sites of Cd-MT are occupied by Cd2+. Cadmium exposure beyond this level gives rise to progressive destabilization of Cd-MT cluster structure in vitro, resulting in increasing proportions of weakly bound, or even unbound, Cd2+ ions. Our results suggest that in vivo, the observed overburdening of Cd-MT with Cd2+ reduces the viability of affected animals.
Institute of Zoology and Limnology, University of Innsbruck, 6020 Innsbruck, Austria.
Monika
M
Chabicovsky
Waltraud
W
Klepal
Reinhard
R
Dallinger
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D006372:Helix, Snails / Q000187:drug effects*; D043143:Hepatopancreas / Q000648:ultrastructure; D006652:Histological Techniques; D008668:Metallothionein / Q000378:metabolism*; D008854:Microscopy, Electron; D013054:Spectrophotometry, Atomic; D013997:Time Factors
D002104:Cadmium; D008668:Metallothionein