γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes.

Defang Ding,Dunhuang Fan,Yun Gao,Linfeng He,Honghong Chen,Jing Wang,Yaping Zhang,Xuxia Zhang,Qiang Li,Xufei Wang

doi:10.1038/srep38295

Abstract

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans.

Highlights

Low-linear energy transfer (LET) radiation[11,12]
We examined the characteristics of the formation, elimination and distribution of the three types of foci, and the status of co-localization of each pair of the three types of foci in human PBLs (HPBLs) exposed to radon and its progeny, and further determined the repair characteristics of the heterochromatic DSBs induced by internal α-particle irradiation from radon and its progeny exposure in HPBLs
The yield of linear γ-H2AX foci tracks was markedly increased over the background level when the absorbed dose from radon exposure was as low as 1.74 mGy, while the yields of linear phosphorylated KAP-1 (pKAP-1) and 53BP1 foci tracks were significantly higher than the corresponding background values only with the cumulative dose of radon reaching 3.39 mGy (Fig. 1B)

Summary

Introduction

Low-LET radiation[11,12]. Recent studies have shown that clustered DSBs can be repaired with slow kinetics via the microhomology-mediated non-homologous end joining (NHEJ) pathway in the G1 phase of the cell cycle[13], and that heterochromatic DSB repair is a critical rate-limiting step in the repair process[13]. Our recent study has established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats, in which the linear γ-H2AX foci track in rat PBLs and bone-marrow lymphocytes (BMLs) can serve as a biomarker to determine whether the body is suffered from high radon exposure in the absence of other internal radiation from α-particle emitting radionuclides and high-LET external irradiation. We examined the characteristics of the formation, elimination and distribution of the three types of foci, and the status of co-localization of each pair of the three types of foci in HPBLs exposed to radon and its progeny, and further determined the repair characteristics of the heterochromatic DSBs induced by internal α-particle irradiation from radon and its progeny exposure in HPBLs. The findings of this study provide an experimental basis for using the γ-H2AX foci-based assay to estimate the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans

Methods

Results

Conclusion