Absorption and Distribution of Cadmium in Metallothionein-I Transgenic Mice

Abstract

Metallothionein-I transgenic (MT-TG) mice have higher concentrations of MT in the stomach (10×), small intestine (4×), large intestine (6×), liver (15×), and kidney (5×) than control mice. The purpose of the present study was to use MT-TG mice to determine whether increased concentrations of MT affect cadmium (Cd) absorption and distribution. A single dose of109Cd was given to control and MT-TG mice orally (0.3–300 μmol/kg, 200 μCi/kg) or intravenously (0.03–10 μmol/kg, 20 μCi/kg). Cd concentrations in 15 tissues were quantified 7 days later. Higher MT concentrations in tissues of MT-TG mice had no appreciable effects on the concentration of Cd in tissues compared to controls. An exception to this was the MT-TG mice given the highest dose of Cd (300 μmol Cd/kg, po), which had twice the tissue Cd concentration of controls. 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 was retained, except for 1–3% at the higher doses (100 and 300 μmol/kg). Cd administered iv distributed mainly to the liver (70%) and kidney (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 μmol/kg. No difference in pattern of Cd distribution to various organs was observed between control and MT-TG mice. These data indicate that higher concentrations of MT in MT-TG mice do not appear to inhibit the gastrointestinal absorption of Cd nor alter the organ distribution of Cd.