Abstract
Metallothionein (MT) is a small-molecular weight, cysteine-rich protein that binds metals. The protective role of
MT in Cd toxicity is well established but its ability to protect against toxicity of other metals remains unclear. 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 only Cd but also Zn, Cu, Fe, Pb, Hg and As. Following daily subcutaneous administration of an
increasing dose of each metal, starting with a low, non-toxic dose, we compared the cumulative median lethal dose
(LD50
) of each metal between wild-type and MT-null mice. The LD50
of Cd for wild-type mice was 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 As. The LD50
of Hg was 1.3-fold higher for wild-type mice than for MT-null mice, but this was
not statistically significant. No difference in LD50
values was observed between wild-type and MT-null mice following
Pb and Fe administration. These results suggest that MT is an important protein in the cellular defense against Cd
toxicity and lethality, but it provides much less protection against the lethality of the other metals. © 2001 Elsevier
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