METALLOTHIONEIN AND TRACE-ELEMENT METABOLISM IN SHEEP TISSUES IN RESPONSE TO HIGH AND SUSTAINED ZINC DOSAGES .1. CHARACTERIZATION AND TURNOVER OF METALLOTHIONEIN ISOFORMS

Romney wether sheep were given ZnO on a regular basis, as required in protocols for the treatment of facial eczema, at either 12 g ZnO fortn ight(-1) or 12 g ZnO week(-1), and the effect of Zn on the synthesis o f different metallothionein (MT) isoforms isolated from liver tissue c haracterized and quantified. Metallothionein isoforms in liver of dose d and non-dosed sheep were quantitatively determined by reverse phase HPLC, with markedly increased concentrations of total MT-Ia protein fo und in the liver tissue of Zn-dosed groups (634 mu g g(-1) fresh weigh t for the weekly dosed group) compared with 49 mu g g(-1) fresh weight in non-dosed sheep. The concentration of MT-II protein was not signif icantly increased. Individual sheep varied widely in the relative amou nts of each MT isoform expressed with increased amounts of types of MT -Ia especially and MT-II in some animals, which bound predominantly Cu . The half-lives for [S-35]-cysteine and Zn-67 in MT isoforms from wee kly dosed sheep were found to be 2.5-3.5 days and 5-24 h respectively, indicating relatively fast exchange of Zn with MT compared with synth esis. Rate of synthesis for MT-Ia was twice that for MT-II. Data refle cting relationships between MT isoforms, Cu and Zn concentrations in l iver are presented and discussed.