Acute cadmium chloride-induced renal toxicity in the Syrian hamster.
It has previously been reported that cadmium (Cd) induces renal lesions only after sequestration by endogenous metallothionein (MT), and not in the form of simple salts. However, in this report we detail findings of acute CdCl2-induced renal lesions in the Syrian hamster, which appear to be species specific as neither rats nor mice showed such lesions. Adult rats and mice of different strains and Syrian hamsters (Cr:RGH) were given Cd doses ranging from 30-50 mumol/kg, sc, and examined histologically for renal lesions between 2 hr and 7 days later. Hamsters developed necrosis of the proximal renal tubules 12-24 hr after CdCl2 treatment at an average incidence of 60% in both sexes. Tubular regeneration occurred within 1 week as shown by immunocytochemical localization of DNA synthesis with 5-bromo-2'-deoxyuridine. By electron microscopy, initial changes with Cd (16 hr) included cytoplasmic vesiculation and dilatation of endoplasmic reticulum, and swelling of mitochondria followed rapidly by enlargement of vacuoles, nuclear changes, and cellular disintegration. Rats and mice showed no such lesions even at lethal doses of Cd (40-50 mumol/kg). At maximum tolerated doses of Cd (approximately LD 10: for rats and mice, 35 mumol/kg; for hamsters, 50 mumol/kg) renal Cd content was not higher in hamsters than in the other species 24 hr after injection; hamsters, in fact, had the lowest Cd content. Likewise, basal or Cd-induced levels of renal MT were not remarkably different between these species. These results indicate the hamster is uniquely susceptible to acute effects of Cd on the kidney and that this effect is not related to an unusually high concentration of CdCl2 or unusually low basal or induced levels of MT in the kidney.
Rehm
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Tumor Pathology and Pathogenesis Section, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701-1013.
Waalkes
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MP
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D019256:Cadmium Chloride; D006224:Cricetinae; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000473:pathology; D008647:Mesocricetus; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D051381:Rats; D011916:Rats, Inbred F344
C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D019256:Cadmium Chloride