First Author | Conrad CC | Year | 2000 |
Journal | Free Radic Biol Med | Volume | 28 |
Issue | 3 | Pages | 447-62 |
PubMed ID | 10699757 | Mgi Jnum | J:61310 |
Mgi Id | MGI:1354670 | Doi | 10.1016/s0891-5849(99)00263-4 |
Citation | Conrad CC, et al. (2000) Using MT(-/-) mice to study metallothionein and oxidative stress. Free Radic Biol Med 28(3):447-62 |
abstractText | Mice with null mutations for metallothionein genes MT-1 and MT-2 were used to study the role that metallothionein plays in protecting cellular targets in vivo from oxidative stress. Wild-type (MT(+/+)) and MT-null (MT(-/-)) mice were treated with either saline or zinc and exposed to two types of oxidative stress: gamma-irradiation or 2-nitropropane. There was no alteration in the antioxidant defense system (superoxide dismutase, catalase, or glutathione peroxidase and glutathione levels) to compensate for the lack of the metallothionein in the MT(-/-) mice. The amount of oxidative damage to liver DNA, lipids, and proteins were similar for the MT(-/-) and MT(+/+) mice even though the levels of metallothionein in the livers of the saline- or zinc-pretreated MT(+/+) mice were 5- to 100-fold greater than found in the MT(-/-) mice. To determine if metallothionein can protect mice from the lethal effects of ionizing radiation, the mean survivals of MT(-/-) and MT(+/+) mice exposed to whole body gamma-irradiation were measured and found to be similar. However, the mean survival increased significantly after zinc pretreatment for both the MT(-/-) and MT(+/+) mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress. |