Development of the stable isotope tracer approach for studies of copper turnover in the rat and mouse.

Abstract The stable isotope tracer approach was explored for long-term investigations of copper turnover in the adult rat and mouse, with inductively coupled plasma mass spectrometry for isotope measurements. The isotopic measurement method permitted precision and accuracy of 65 Cu. Compared with the baseline isotope ratio ( 65 Cu/ 63 Cu) of 0.462 ± 0.002, blood plasma ratios for the +Cu group on days 2, 7, and 14 postdosing were 0.702 ± 0.021, 0.557 ± 0.004, and 0.474 ± 0.001, respectively. The corresponding data for liver were 0.652 ± 0.018, 0.560 ± 0.005, and 0.482 ± 0.001, respectively. For the −Cu group, respective plasma ratios were 1.580 ± 0.04, 0.917 ± 0.02, and 0.664 ± 0.01 for days 2, 7, and 14 postdosing, and the ratios for liver were 0.978 ± 0.02, 0.876 ± 0.04, and 0.739 ± 0.03. Mice previously made copper deficient to varying degrees were given a single-day replacement with the label. When the 24-hour postdosing isotope ratios in the livers of these mice were correlated with the activity of plasma ceruloplasmin, a negative correlation ( r = −0.85) was observed. Isotope enrichment in both rats and mice was greater in the copper-deficient animals compared with the controls.