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首页> 外文期刊>Cell cycle >Histone H2AX phosphorylation after cell irradiation with UV-B: relationship to cell cycle phase and induction of apoptosis.
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Histone H2AX phosphorylation after cell irradiation with UV-B: relationship to cell cycle phase and induction of apoptosis.

机译：UV-B照射细胞后组蛋白H2AX磷酸化：与细胞周期阶段和凋亡诱导的关系。

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Damage to DNA that engenders double-strand breaks (DSBs) triggers phosphorylation of histone H2AX on Ser-139. Expression of phosphorylated H2AX (gammaH2AX) can be revealed immunocytochemically; the intensity of gammaH2AX immunofluorescence (IF) measured by cytometry was reported to correlate with the frequency of DSBs induced by X-ray radiation or by DNA damaging antitumor drugs. The aim of the present study was to measure expression of gammaH2AX following exposure of HeLa and HL-60 cells to a wide range of doses of UV-B light (6.1 J/m(2)-3.45 kJ/m(2)) and using multiparameter flow and laser scanning cytometry (LSC) to correlate DNA damage with cell cycle phase and induction of apoptosis. In both cell lines, the highest degree of H2AX phosphorylation induced by UV was seen in S-phase cells, particularly during early portion of S. In cells that did not replicate DNA (G(1), G(2) and M) the degree of H2AX phosphorylation was markedly lower than that in S-phase cells, and was strongly UV dose-dependent. Furthermore, the level of UV-induced gammaH2AX in G(1), G(2) and M was much higher in HeLa- than in HL-60- cells. Apoptotic cells become apparent >2h after exposure to UV and exhibited nearly an order of magnitude higher intensity of gammaH2AX IF than that initially induced by UV; predominantly S-phase cells underwent apoptosis. While the suppression of DNA replication, by aphidicolin prevented the induction of H2AX phosphorylation by UV in most S phase cells, it had no effect on a small cohort of cells that appeared to be entering S-phase, that expressed very high levels of gammaH2AX. Furthermore, aphidicolin itself induced gammaH2AX in early-S phase cells. The induction of gammaH2AX by UV was inhibited, but the incidence of apoptosis increased, by 5 mM caffeine, a known inhibitor of PI-3-related kinases. The data are consistent with the notion that H2AX phosphorylation observed throughout S phase reflects formation of DSBs due to the collision of replication forks with the UV-induced primary DNA lesions. Induction of gammaH2AX in G(1), G(2) and M is likely a response to the primary DSBs generated during UV exposure and/or DNA repair. It is unclear why the latter process was more pronounced in HeLa than in HL-60 cells.
机译：导致双链断裂（DSB）的DNA损伤会触发Ser-139上组蛋白H2AX的磷酸化。磷酸化的H2AX（gammaH2AX）的表达可以通过免疫细胞化学方法揭示;据报道，通过流式细胞仪测量的gammaH2AX免疫荧光强度（IF）与X射线辐射或DNA破坏性抗肿瘤药物诱导的DSB频率相关。本研究的目的是测量HeLa和HL-60细胞暴露于各种剂量的UV-B光（6.1 J / m（2）-3.45 kJ / m（2））和之后的gammaH2AX表达。使用多参数流和激光扫描细胞仪（LSC）将DNA损伤与细胞周期阶段和凋亡诱导相关联。在这两种细胞系中，在S期细胞中，特别是在S期早期，可见由UV诱导的H2AX磷酸化程度最高。在不复制DNA的细胞（G（1），G（2）和M）中， H2AX磷酸化程度显着低于S期细胞，并且强烈依赖于紫外线剂量。此外，HeLa-中的紫外线诱导的GammaH2AX在G（1），G（2）和M中的水平要比HL-60-细胞高得多。凋亡细胞在暴露于紫外线后> 2h时变得明显，并显示出比最初由紫外线诱导的强度高近一个数量级的gammaH2AX IF。 S期细胞主要发生凋亡。在大多数S期细胞中，虽然蚜虫可抑制DNA复制，阻止了UV诱导H2AX磷酸化，但对一小部分似乎进入S期的细胞却没有影响，这些细胞表达了很高的gammaH2AX水平。此外，蚜虫素本身在早期S期细胞中诱导了gammaH2AX。 UV抑制了gammaH2AX的诱导，但是5 mM咖啡因（一种已知的PI-3相关激酶抑制剂）增加了细胞凋亡的发生率。数据与以下观点一致：在整个S期观察到的H2AX磷酸化反映了由于复制叉与UV诱导的初级DNA损伤的碰撞而形成的DSB。 G（1），G（2）和M中的gammaH2AX诱导可能是对紫外线暴露和/或DNA修复过程中产生的主要DSB的反应。目前尚不清楚为什么后者在HeLa中比在HL-60细胞中更明显。

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