毒理学相关资料,第五章内容参考文献40.pdfVIP

Toxicology 163 (2001) 93–100 /locate/toxicol Protective effect of metallothionein against the toxicity of cadmium and other metals 1 Jung D. Park 2, Yaping Liu, Curtis D. Klaassen * Department of Pharmacology, Toxicology Therapeutics, Uniersity of Kansas Medical Center, Kansas City, KS 66160-7417, USA Received 13 December 2000; received in revised form 5 March 2001; accepted 6 March 2001 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 agai