Absorption and distribution of cadmium in metallothionein-I transgenic mice.
Metallothionein-I transgenic (MT-TG) mice have higher concentrations of MT in the stomach (10x), small intestine (4x), large intestine (6x), liver (15x), and kidney (5x) 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 of 109Cd was given to control and MT-TG mice orally (0.3-300 mumol/kg, 200 microCi/kg) or intravenously (0.03-10 mumol/kg, 20 microCi/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 mumol 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 mumol/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 mumol/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.
Liu
J
J
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160, USA.
Klaassen
C D
CD
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D019256:Cadmium Chloride; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D005753:Gastric Mucosa / Q000378:metabolism; D007275:Injections, Intravenous; D007420:Intestine, Large / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011863:Radioimmunoassay; D014018:Tissue Distribution
D002273:Carcinogens; D002712:Chlorides; D002104:Cadmium; D008668:Metallothionein; D019256:Cadmium Chloride