Metallothionein in radiation exposure: its induction and protective role

Since its discovery about 40 years ago, there has been a wide interdisciplinary research interest in metallothionein (MT) on its physiological and toxicological aspects. Functionally, MT is involved not only in metal detoxification and homeostasis, but also in scavenging free radicals during oxidative damage. Among over 4500 publications which can be retrieved by Medline search, only about 50 reports have been published on the relationship of MT with ionizing and UV radiation. In this review, we have evaluated critically the published data on the induced synthesis of MT by radiation, and the potential functions of MT in radiation induced cell damage. MT mRNA expression or MT synthesis was found to be induced by exposure of cells in vitro or tissues in vivo to ionizing or UV radiation. In most of the studies in animals and tissue cultures, high doses of ionizing radiation were used to induce MT, and, therefore, it is difficult to extrapolate these results to low level of repeated exposures to radiation in humans. Induced synthesis of MT is considered as one of the mechanisms involved in the adaptive response to low dose radiation exposure. The presence of MT in normal cells may provide protective effects from radiation-induced genotoxicity and cytotoxicity. However, in tumor cells, the presence of MT can result in drug and radiation resistance as well. These effects are modulated by other cellular factors, besides MT, such as antioxidants, and by the cell cycle stages in cell proliferation and differentiation.