New mechanism of gamma-H2AX generation: Surfactant-induced actin disruption causes deoxyribonuclease I translocation to the nucleus and forms DNA double-strand breaks

作者：Zhao Xiaoxu; Yang Gang; Toyooka Tatsushi; Ibuki Yuko

来源：Mutation Research: Genetic Toxicology and Environmental Mutagenesis , 2015, 794: 1-7.

DOI：10.1016/j.mrgentox.2015.09.006

• Nonylphenol polyethoxylates
• Deoxyribonuclease I
• Actin
• DNA double-strand breaks
• gamma-H2AX
• Surfactants

We previously showed that nonionic surfactants, nonylphenol polyethoxylates (NPEOs), induced phosphorylation of histone H2AX, forming gamma-H2AX. In this study, we analyzed the mechanism of gamma-H2AX generation by an NPEO with 15 ethylene oxide units (NPEO(15)). In MCF-7 breast carcinoma cells, NPEO(15) treatment induced gamma-H2AX in a dose-dependent manner. EDTA and ZnCl2, two inhibitors of deoxyribonuclease I (DNase I), inhibited both the gamma-H2AX and DNA double-strand breaks induced by NPEO(15). NPEO(15) disrupted filamentous actin and released free DNase I as detected by cell fractionation analysis. Based on immunofluorescence staining of DNase I and monitoring DNase I-GFP localization, DNase I was translocated from the cytosol to the nucleus of cells after treatment with NPEO(15). This translocation did not occur with the common DNA damage inducers ultraviolet B irradiation and hydrogen peroxide. Other surfactants, Tween 20, Triton X-100 and Nonidet P-40, also generated gamma-H2AX. These results show that gamma-H2AX induction by surfactants including NPEOs, occurs via a new mechanism involving release of free DNase I with actin disruption. This mechanism is distinct from the process of gamma-H2AX generation caused by direct chemically induced DNA damage.

• 出版日期2015-12
• 单位国家安全生产监督管理总局信息研究院