Modulation of ionizing radiation-induced effects by NU7441, KU55933 and VE821 in peripheral blood lymphocytes

Journal of Applied Biomedicine

关键词: Ionizing radiation;    Lymphocytes;    KU55933;    NU7441;    VE821;    ATMataxia-telangiectasia mutated kinase;    ATRataxia telangiectasia and Rad3-related protein kinase;    DMSOdimethyl sulfoxide;    DNA-PKDNA-dependent protein kinase;    DSBdouble strand break;    Gygray;    MFImedian fluorescence intensity;    MNmicronuclei;    NBUDnuclear bud;    NHEJnon homologous end-joining;    NPBnucleoplasmatic bridge;    PI3-Kphosphatidylinositol 3-kinase;    SEMstandard error of mean;   

DOI  :  10.1016/j.jab.2015.07.001

学科分类：医学（综合）

来源: Elsevier

【 摘 要 】

We evaluated the impact of ataxia-telangiectasia mutated kinase inhibitor KU55933, DNA-dependent protein kinase inhibitor NU7441 and ataxia telangiectasia and rad3-related kinase inhibitor VE821 in human peripheral lymphocytes in vitro. The lymphocytes were divided into 5 groups: non-irradiated control, irradiated group (2 Gy) and 3 groups pretreated with inhibitors 30 min before irradiation. We used flow cytometry to evaluate phosphorylated H2AX (γ-H2AX) and cytotoxicity (Apoptest). Micronucleus assay was used to assess genotoxicity. After irradiation, γ-H2AX, incidence of micronuclei (MN), nucleoplasmatic bridges (NPBs) and nuclear buds in binuclear cells, MN in mononuclear cells and apoptosis were increased. KU55933 decreased γ-H2AX and inhibited ionizing radiation-induced cytotoxicity. NU7441 showed no effect on γ-H2AX but it significantly increased MN and NPBs in binuclear cells and apoptosis. VE821 decreased γ-H2AX, whereas genotoxicity and cytotoxicity were not affected. In conclusion, KU55933 protected lymphocytes, which might be employed to preserve the immune system during anticancer therapy. NU7441 radiosensitized lymphocytes, thus, undesirable side effects toward immune system could be expected. VE821 showed decrease of γ-H2AX with no radiosensitizing effects in our model likely due to p53 positive status, which underlies the concept of its application in p53 negative environment.

【 授权许可】

Unknown