Effect of 67Cu and 99Mo labeled tetrathiomolybdate on the distribution of 67Cu, Cu, and 99Mo in bile fractions in sheep.

The effect of intravenous administration of 67Cu and 99Mo labeled tetrathiomolybdate (TTM) on the appearance of 67Cu, stable Cu, and 99Mo in gel chromatographic fractions of bile was examined in sheep fed either 5 or 35 mg Cu kg-1 DM. Peak excretory periods of biliary 67Cu, stable Cu, and 99Mo were observed at 30 min-1.25 hr, 2-3 hr, and 11-13 hr after 67Cu and after 99Mo labeled TTM. Sephadex G-75 gel filtration of bile samples collected at 1, 3, and 12 hr after 67Cu administration revealed two major protein peaks of molecular weights of greater than 80,000 (peak I) and 7,000 (peak II) containing both 67Cu and Cu. But the ratio of 67Cu in the two peaks varied with time of bile collection. The ratio of areas of peak I:II 1 hr after 67Cu administration was approximately 0.48; at 3 hr, 0.62, and at 12 hr 1.35. Tetrathiomolybdate administration increased both 67Cu and stable Cu in bile by severalfold and induced a major shift of Cu into the higher molecular weight protein fraction. The experiments confirm the effectiveness of TTM as a "decoppering" agent. Furthermore, TTM not only promoted bile Cu excretion, but it also increased the incorporation of Cu into the macromolecular fraction. This may limit enterohepatic circulation of biliary Cu and thereby cause an overall Cu depletion and a negative Cu balance.