resumo
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 (CdCl2), may induce microsatellite mutations in murine testes. For this study, 2-month-old male ICR-CDI mice were treated by a single subcutaneous injection of I, 2 and 3 mg CdCl2/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 CdCl2 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 CdCl2 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.
palavras-chave
MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; MISMATCH REPAIR; CARCINOGENESIS; TOXICITY; CELLS; RATS; METALLOTHIONEIN; TRANSPORTER; MECHANISMS
categoria
Toxicology
autores
Oliveira, H; Lopes, T; Almeida, T; Pereira, MD; Santos, C
nossos autores
Helena Oliveira
Bolseiro de pós-Doutoramento
Maria de Lourdes Gomes Pereira
Professor Associado com Agregaçãoagradecimentos
The work of H. Oliveira was supported by FCT (grant reference SFRH/BPD/48853/2008). This work was supported in part by Centre for Research in Ceramics and Composite Materials from Aveiro University (Portugal).