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Cadmium-induced genetic instability in mice testis.

Abstract
Cadmium is a well recognized carcinogenic, cytotoxic and mutagenic transition metal. Recent evidence suggests that the proteins participating in the DNA repair systems, especially in excision and mismatch repair (MMR), are sensitive targets of cadmium toxicity. Microsatellite instability (MSI) is regarded as one of the phenotypes of defective DNA MMR and, consequently, as a marker of high risk for cancer. The purpose of this work is to determine whether cadmium, in the form of cadmium chloride (CdCl(2)), may induce microsatellite mutations in murine testes. For this study, 2-month-old male ICR-CD1 mice were treated by a single subcutaneous injection of 1, 2 and 3 mg CdCl(2)/kg body weight and killed after 35 days. A panel of six microsatellite markers, previously reported as being the most sensitive in detecting MSI in murine tumours, was used in this study. The results show that CdCl(2) in the doses of 2 and 3 mg/kg induced a decrease in the testis weight and severe histopathologic changes with complete disorganization of testicular structure and evidences of severe necrosis. In addition, the animals exposed to the lowest CdCl(2) dose presented MSI in the testis. The results indicate the existence of MSI in at least two nuclear loci suggesting putative genotoxic effects induced by cadmium.
AuthorsHelena Oliveira, Tina Lopes, Tânia Almeida, Maria de Lourdes Pereira, Conceição Santos
JournalHuman & experimental toxicology (Hum Exp Toxicol) Vol. 31 Issue 12 Pg. 1228-36 (Dec 2012) ISSN: 1477-0903 [Electronic] England
PMID22699117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Mutagens
  • Cadmium Chloride
Topics
  • Animals
  • Body Weight (drug effects)
  • Cadmium Chloride (toxicity)
  • DNA Mismatch Repair (drug effects)
  • Dose-Response Relationship, Drug
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microsatellite Instability (drug effects)
  • Mutagens (toxicity)
  • Organ Size (drug effects)
  • Testis (drug effects, pathology)

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