title: Cadmium-induced genotoxicity in human osteoblast-like cells.
abstract: Cadmium (Cd) is a widespread heavy metal used in numerous industrial processes. Cd exerts toxicological effects mostly in kidney and liver. Bone is also an important target of Cd, however, the cellular mechanisms of Cd toxicological effects in the bone cells are still poorly understood. Therefore, the present work aimed to investigate the putative cytotoxic and genotoxic effects of Cd to human bone cells. For that, the osteoblast-like MG-63 cells were exposed to 20 and 50μM Cd for 24 and 48h. Results showed a dose-dependent increase in Cd accumulation in cells and a decrease in cell viability, especially after 48h. Cell cycle analysis showed a delay at S phase concomitant with a decrease in cells at G0/G1 phase. After 24h, Cd treatment downregulated the expression of CHEK1, CHEK2 and CDK2 genes and upregulated the expression of CCNE1 gene. After 48h, the expression of ATM and CCNB1 genes were downregulated. Also, a 3.3 fold increase on the expression of gene CCNE1 was detected. Both Cd doses induced DNA fragmentation at 48h, while an increase in micronuclei (MN) and nucleoplasmic bridges (NPBs) together with an increase in the percentage of apoptotic/necrotic cells was detected for both time periods. Overall, our results demonstrate the cytotoxicity and genotoxicity of Cd in human bone cells. Also, the cytokinesis-block micronucleus (CBMN) assay parameters (MN, NPBs and the percentage of cells under apoptosis or necrosis) together with the cell cycle appear as the most sensitive to Cd cyto- and genotoxicity, being early affected even with the lowest Cd dose. Therefore, these cyto-/genotoxic techniques may be selected for early detection of Cd-induced toxicity.
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: holiveira@ua.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Monteiro
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pinho
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Pinho
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: José Miguel P
authors.initials: JM
authors.lastname: Ferreira de Oliveira
authors.affiliation: CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Conceição
authors.initials: C
authors.lastname: Santos
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015162:Micronucleus Tests / Q000379:methods; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*
chemical_list: D002104:Cadmium
keywords: Cadmium; Cell cycle; Cytotoxicity; DNA damage; Genotoxicity; Micronuclei