C. elegans metallothioneins: new insights into the phenotypic effects of cadmium toxicosis.

Metallothioneins are considered to be the primary player in the detoxification of and protection from cadmium, a teratogen, mutagen and potentially lethal heavy metal. The nematode Caenorhabditis elegans has only two metallothioneins, mtl-i and mtIl-2, thus making it an ideal organism to investigate the phenotypic effects of cadmium toxicosis. The functional importance of metallothioneins in cadmium trafficking was highlighted through the generation of viable green fluorescent protein (GFP) expressing transgenes, a metallothionein null allele, as well as RNAi mediated metallothionein knock-downs. A highly sensitive dose and temporal transcriptional response to cadmium, but not copper or zinc, was shown to be equally prevalent in both isoforms. No measurable compensatory up-regulation of mtl-l could be observed in the null allele of mtl-2, suggesting that both isoforms are independent and not synergistic in their mode of action. Exposure to cadmium affected all demographic indices measured, manifested by a reduction in body size, generation time, brood size and lifespan. These effects were magnified in the knock-out or wild-type subjected to a knock down by RNAi, however, only in the presence of cadmium. This substantiates the notion that metallothioneins play a pivotal role in the protection from cadmium toxicosis. Finally, an earthworm metallothionein-GFP construct could be activated in C. elegans upon exposure to cadmium, the results providing further evidence that the transcriptional control of metallothioneins is fundamentally divergent in lower invertebrates and not mediated via MTF-1 as in more complex organisms. Copyright 2004 Elsevier Ltd.