Cd-metallothionein nephrotoxicity in inbred strains of mice.
Genetic differences in the acute hepatic and testicular toxicity of Cd occur among different strains of mice. However, it is not known whether genetic variation to the renal damage caused by Cd-metallothionein (CdMT) exists. Therefore, male mice of the C3H/HeJ, C57/Bl10, CBA/CA, and DBA/2J strains, previously shown to differ in hepatic and testicular injury due to Cd, were treated with CdMT at dosages of 0.2, 0.4, 0.8, and 1.6 mg/kg (sc). For all strains of mice, tissue accumulation of Cd occurred predominantly in kidney, which had two to three times as much Cd as liver, while testes had no measurable amounts of Cd. Hepatic and renal metallothionein (MT) concentrations were increased with increasing dosage of CdMT, and no differences between strains were demonstrated. Urinary glucose was increased significantly at the three highest dosages of CdMT, with no differences between strains. At each dose level, light microscopic manifestations of CdMT nephropathy did not differ between strains. In summary, all CdMT-treated strains of mice responded similarly with respect to all measured renal parameters (accumulation of Cd and MT and nephrotoxicity). Unlike the strain differences in hepatic and testicular injury from Cd in these strains of mice, CdMT nephrotoxicity shows no such genetic variation.
Sendelbach
L E
LE
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Kershaw
W C
WC
Cuppage
F
F
Klaassen
C D
CD
D000818:Animals; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D008811:Mice, Inbred DBA / Q000235:genetics; D013045:Species Specificity; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution
C004203:cadmium-binding protein; D008668:Metallothionein