DISTRIBUTION AND RETENTION OF CADMIUM IN METALLOTHIONEIN-I AND METALLOTHIONEIN-II NULL MICE

Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its binding to metallothionein (MT). This study was d esigned to determine the role of MT in the tissue distribution and ret ention of Cd using MT-I and -II null (MT-null) mice. Mice were given ( CdCl2)-Cd-109 (15 mu mol/kg, 25 mu Ci/kg, ip), and radioactivity was q uantified in 14 major organs at 2 hr, 1, 2, 3, 7 and 15 days thereafte r. The lack of MT in MT-null mice did not affect the initial tissue di stribution of Cd, as similar amounts of Cd were distributed in control (C57BL/6J) and MT-null mice 2 hr after Cd administration (74% vs 72% of the dose, respectively). However, the elimination of Cd was much fa ster in MT-null mice than in control mice. In control mice, approximat ely 40% of Cd administered was found in liver 24 hr after administrati on, and the majority was bound to MT. In contrast, only 20% of Cd was found in liver of MT-null mice, which was not bound to MT. Cd concentr ations in kidney, pancreas, and spleen were also lower in MT-null than in control mice 1 week after administration. No apparent difference i n Cd retention in other organs was noted between control and MT-null m ice over the 15-day period. Cd concentration in kidney continued to in crease with time in control but not in MT-null mice, indicating that a n important source of Cd in the kidney is the uptake of CdMT. In concl usion, the present data indicate that MT does not play a role in the i nitial distribution of Cd to tissues, but does play a major role in th e elimination of Cd, especially from liver, kidney, and pancreas. Thes e data support the conclusion that the persistence of Cd in the body i s at least partially due to Cd binding to MT in tissues. (C) 1996 Acad emic Press, Inc.