ABSORPTION AND DISTRIBUTION OF CADMIUM IN METALLOTHIONEIN-I TRANSGENIC MICE

Metallothionein-I transgenic (MT-TG) mice have higher concentrations o f MT in the stomach (10X), small intestine (4X), large intestine (6X), liver (15X), and kidney (5X) than control mice. The purpose of the pr esent study was to use MT-TG mice to determine whether increased conce ntrations of MT affect cadmium (Cd) absorption and distribution. A sin gle dose of Cd-109 was given to control and MT-TG mice orally (0.3-300 mu mol/kg, 200 mu Ci/kg) or intravenously (0.03-10 mu mol/kg, 20 mu C i/kg). Cd concentrations in 15 tissues were quantified 7 days later. H igher MT concentrations in tissues of MT-TG mice had no appreciable ef fects on the concentration of Cd in tissues compared to controls. An e xception to this was the MT-TG mice given the highest dose of Cd (300 mu mol Cd/kg, po), which had twice the tissue Cd concentration of cont rols. Approximately 60% of the Cd administered iv was retained in the tissues; retention of Cd in MT-TG mice was similar to that in controls . In both control and MT-TG mice only 0.1-0.3% of Cd administered po w as retained, except for 1-3% at the higher doses (100 and 300 mu mol/k g). Cd administered iv distributed mainly to the liver (70%) and kidne y (10%) and was independent of dose. In contrast, when administered po , distribution of Cd to the liver increased from 40 to 75% of the dose , whereas distribution to kidney decreased from 30 to 7% as doses were increased from 0.3 to 300 mu mol/kg. No difference in pattern of Cd d istribution to various organs was observed between control and MT-TG m ice. These data indicate that higher concentrations of MT in MT-TG mic e do not appear to inhibit the gastrointestinal absorption of Cd nor a lter the organ distribution of Cd. (C) 1996 Society of Toxicology