title: Susceptibility of metallothionein-null mice to paraquat.
abstract: Using transgenic mice in which metallothionein (MT)-I and MT-II genes, we have studied a putative role of MT as a free radical scavenger against paraquat, a free radical generator. Male mice were injected s.c. with paraquat (PQ) at a single dose of 40 or 60 mg/kg of body weight (b.w.). Two of the six MT-null mice died within 16 h at the dose of 60 mg PQ/kg. b. w. PQ administration increased hepatic MT concentration in the normal mice (C57BL/6J), but not in the MT-null mice. The lipid peroxidation (LP) determined by thiobarbituric acid-reactive substance formation was increased by PQ in the liver of normal and MT-null mice, and the enhanced level was greater in the MT-null mice than in the C57BL/6J mice. Administration of PQ significantly increased blood urea nitrogen only in the MT-null mice, indicating renal damage. Without paraquat administration, the hepatic concentration of non-protein sulphydryl compounds was less in the MT-null mice than in the C57BL/6J mice, and the basal level of LP was higher in the MT-null mice than in the C57BL/6J mice. The present results support the notion that MT plays an antioxidative role against paraquat insult under physiological conditions.
authors.affiliation: Institute of Biomedical Sciences, Fukushima Medical College, Fukushima 960-12, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: M D
authors.initials: MD
authors.lastname: Apostolova
authors.forename: M
authors.initials: M
authors.lastname: Hamaya
authors.forename: J
authors.initials: J
authors.lastname: Yamaki
authors.forename: K H
authors.initials: KH
authors.lastname: Choo
authors.forename: A E
authors.initials: AE
authors.lastname: Michalska
authors.forename: N
authors.initials: N
authors.lastname: Kodama
authors.forename: C
authors.initials: C
authors.lastname: Tohyama