Long-term measurement of organ copper turnover in rats by continuous feeding of a stable isotope.

Utilizing the continuous feeding of a single stable isotope and inductively coupled plasma mass spectrometry, we have developed a method that allows the measurement of organ copper turnover in the rat for at least 8 weeks. Previous methods, based on tracer studies using radioisotopes of copper, were severely limited by the short half-lives of the radioisotopes (12.8 and 61.8 h). Taking advantage of the known ratio of the two naturally occurring stable isotopes of copper (63Cu and 65Cu), dietary copper was replaced by a single isotope of copper (63Cu) for the entire 8-week period. Disappearance of the other isotope (65Cu) from tissues was then monitored as a measure of copper turnover. Because this method is not a tracer study, it has the unique advantage of uniformly labeled physiological and kinetic compartments. Half-lives of individual first-order kinetic compartments within organs and plasma were obtained by analysis of the 8-week copper turnover curves in copper-adequate and copper-restricted rats. Mean decreases in organ copper following 56 days of copper restriction were plasma, 99%; liver, 62%; heart, 3%; muscle, 26%; kidney, 66%; and brain, < 1%. Comparison of normal organ turnover to turnover in copper-restricted rats revealed that this method can be used during periods of severe copper restriction and that copper conservation during these periods is organ specific.