Protective effect of metallothionein against the toxicity of cadmium and other metals

Metallothionein (MT) is a small-molecular weight. cysteine-rich protein tha t binds metals. The protective role of MT in Cd toxicity is well establishe d but its ability to protect against toxicity of other metals remains uncle ar. In this study, wild-type and MT-I and -II null mice (MT-null mice) were used to determine whether MT is protective against the lethality of not on ly Cd but also Zn, Cu, Fe, Pb. Hg and As. Following daily subcutaneous admi nistration of an increasing dose of each metal, starting with a low, non-to xic dose, rye compared the cumulative median lethal dose (LD50) of each met al between wild-type and MT-null mice. The LD50 of Cd for wild-type mice wa s 6.9-fold higher than for MT-null mice. The LD50 of Zn was 2.4-fold higher for wild-type mice than for MT-null mice, and 1.4-fold higher for Cu and A s. The LD50 of Hg was 1.3-fold higher for wild-type mice than for MT-null m ice, but this was not statistically significant. No difference in LD50 valu es was observed between wild-type and MT-null mice following Pb and Fe admi nistration. These results suggest that MT is an important protein in the ce llular defense against Cd toxicity acid lethality, but it provides much les s protection against the lethality of the other metals. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.