Cr(VI)‐induced genotoxicity and cell cycle arrest in human osteoblast cell line MG‐63

遗传毒性 微核试验 彗星试验 DNA损伤 细胞周期 活力测定 微核 细胞周期检查点 细胞分裂 化学 细胞 细胞生长 染色体畸变 分子生物学 DNA修复 毒性 生物 医学 内科学 生物化学 DNA 染色体 基因
作者
Cristina Monteiro,Conceição Santos,Verónica Bastos,Helena Oliveira
出处
期刊:Journal of Applied Toxicology [Wiley]
卷期号:39 (7): 1057-1065 被引量:13
标识
DOI:10.1002/jat.3793
摘要

Abstract Occupational environments are major exposure routes to Cr(VI). However, Cr(VI) may also establish in bone tissues by ingestion or through Cr containing orthopaedic prostheses that, due to wear and corrosion, may release metal particles and ions potentially affecting bone tissue. The aim of this work was to evaluate the effects of clinically relevant concentrations of Cr(VI) in human osteoblasts, by integrating genotoxic effects, evaluated by the comet assay and cytokinesis‐blocked micronucleus assay (scoring the presence of micronucleus, nucleoplasmic bridges and nuclear division index), with the effects on cell cycle and cell viability. Human osteoblasts MG‐63 were in vitro exposed to Cr(VI) at concentrations ranging from 0.1 to 5 μ m , for 24 and 48 hours. Results pointed out to a decrease of cell viability for both time exposures in a time‐ and dose‐dependent manner, which was related to cell cycle arrest and DNA damage. Chromosome abnormalities were also observed. Hence, these data suggest that cells arrested in the cell division with DNA damage may have followed cell death pathways, while some surviving ones still revealed DNA damage at chromosome level indicating abnormal cell division progression. In conclusion, Cr(VI) induced cytotoxic and genotoxic effects in human bone cells at concentrations that could be found in patients with metal‐on‐metal prostheses. In addition, the early onset of genotoxic damage induced by Cr(VI) at low concentrations after 24 hours of cell exposure alert to the relevance of periodic monitoring of patients for genotoxicity diagnosis after implantation of prostheses before clinical symptoms appear.
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