Toxicological significance of metallothionein on environmental harmful factors: verification and suggestions from a metallothionein-I/II null mouse model study

Abstract

In many research groups including our laboratory, metallothionein (MT)-I/II null mice have been used to clarify the biological function and physiological role of MT. Recent studies with MT-I/II null mice concerning the role of MT in the toxicity and distribution of metal, oxidative stress and chemical carcinogenesis were reviewed. Some reports, including our findings, showed that MT-I/II null mice have an increased sensitivity to harmful metals such as cadmium, mercury, zinc and arsenic. Moreover, it was clarified using MT-I/II null mice that MT plays a major role in the retention of cadmium, mercury and zinc in target tissues. MT-I/II null mice were found to be much more sensitive than wild-type mice to the toxicity caused by free radical-inducing factors, which include paraquat, acetaminophen, ethanol, X-ray, ultraviolet B, carbon tetrachloride, cisplatin, doxorubicin, cerulein and streptozotocin. In addition, MT-I/II null mice were highly susceptible to skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene and bladder carcinogenesis caused by N-butyl-N-(4-hydroxybutyl)nitrosamine. These results suggest that MT is an important protective factor against metal toxicity, oxidative stress and chemical carcinogenesis.