In vitro genotoxicity of airborne Ni-NP in air-liquid interface

被引:17
作者
Latvala, Siiri [1 ]
Vare, Daniel [2 ]
Karlsson, Hanna L. [3 ]
Elihn, Karine [1 ]
机构
[1] Stockholm Univ, Atmospher Sci Unit, Dept Environm Sci & Analyt Chem, SE-10691 Stockholm, Sweden
[2] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden
[3] Karolinska Inst, Inst Environm Med, Div Biochem Toxicol, SE-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
air-liquid interface; alkaline DNA unwinding; DNA damage; HPRT; nanotoxicology; SB; CHINESE-HAMSTER CELLS; EXPOSURE SYSTEM; LUNG-CANCER; DNA-REPAIR; METAL-IONS; NICKEL; TOXICITY; NANOPARTICLES; MECHANISMS; MUTATION;
D O I
10.1002/jat.3510
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively. Additionally, co-exposure to a PARP-1 inhibitor was performed to test possible involvement of base excision repair (BER) in repair of Ni-induced DNA damage. The results showed that cell viability was reduced significantly (to 45% and 46%) after 48hours Ni-NP exposure at concentrations of 0.15 and 0.32g cm(-2). DNA damage was significantly increased after Ni-NP exposure in the presence of the BER inhibitor indicating that Ni-NP-induced DNA damages are subsequently repaired by BER. Furthermore, there was no increased HPRT mutation frequency following Ni-NP exposure. In conclusion, this study shows that Ni-NP treatment of lung fibroblasts in an air-liquid interface system that mimics real-life exposure, results in increased DNA strand breaks and reduced cellular viability. These DNA lesions were repaired with BER in an error-free manner without resulting in mutations. This study also underlines the importance of appropriate quantification of the actual exposure concentrations during air-liquid interface exposure studies. The aim of this study was to investigate the genotoxicity of airborne Ni nanoparticles using a recently developed air-liquid interface exposure system that mimics real-life exposure. Cytotoxicity, DNA damage and mutagenicity were in the V79 cell line. Ni nanoparticle exposure of the cells in the air-liquid interface resulted in increased DNA strand breaks and reduced cellular viability at concentrations of 0.15 and 0.32 g cm (-2). These DNA lesions were repaired with BER in an error-free manner without resulting in mutations
引用
收藏
页码:1420 / 1427
页数:8
相关论文
共 34 条
  • [11] FORD DK, 1958, JNCI-J NATL CANCER I, V21, P393
  • [12] Exposure to different forms of nickel and risk of lung cancer
    Grimsrud, TK
    Berge, SR
    Haldorsen, T
    Andersen, A
    [J]. AMERICAN JOURNAL OF EPIDEMIOLOGY, 2002, 156 (12) : 1123 - 1132
  • [13] Interference by toxic metal ions with DNA repair processes and cell cycle control:: Molecular mechanisms
    Hartwig, A
    Asmuss, M
    Ehleben, I
    Herzer, U
    Kostelac, D
    Pelzer, A
    Schwerdtle, T
    Bürkle, A
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 2002, 110 : 797 - 799
  • [14] HARTWIG A, 1995, BIOMETALS, V8, P3
  • [15] Helleday T, 2000, ENVIRON MOL MUTAGEN, V35, P114, DOI 10.1002/(SICI)1098-2280(2000)35:2<114::AID-EM6>3.0.CO
  • [16] 2-Q
  • [17] ATR signaling mediates an S-phase checkpoint after inhibition of poly(ADP-ribose) polymerase activity
    Horton, Julie K.
    Stefanick, Donna F.
    Kedar, Padmini S.
    Wilson, Samuel H.
    [J]. DNA REPAIR, 2007, 6 (06) : 742 - 750
  • [18] IARC, 1990, IARC MONOGRAPHS EVAL, V49
  • [19] International Commission on Radiological Protection (ICRP), 1994, HUM RESP TRACT MOD R, V66
  • [20] Jenssen D., 1984, HDB MUTAGENICITY TES, P269