Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities.
Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities.
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DOI：
10.1269/jrr.08109
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发表时间：
2009-03
影响因子：
2
通讯作者：
Tomohiro Yoshikawa;G. Kashino;K. Ono;M. Watanabe
中科院分区：
文献类型：
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作者：
Tomohiro Yoshikawa;G. Kashino;K. Ono;M. Watanabe
电离辐射引起DNA双链断裂，引起染色体改变，染色质蛋白质发生改变。组蛋白H2 AX被磷酸化，磷酸化的H2 AX成为焦点。磷酸化的H2 AX灶被认为是DNA双链断裂修复因子的募集介质。虽然大多数初始磷酸化的H2 AX灶随着DNA DSB的修复而消失，但仍有少数灶保留，并且这些残留的DSB是否与放射敏感性相关尚不清楚。因此，我们研究了电离辐射后残留DSB和细胞辐射敏感性之间的相关性。我们发现，一半的未照射的正常细胞有几个磷酸化的H2 AX灶不断，和大多数细胞照射不到1%的集落形成剂量的磷酸化H2 AX灶，即使在照射后5天。一些肿瘤细胞系甚至在非照射条件下也具有磷酸化的H2 AX灶。这些结果表明，在正常细胞系中，照射后残留的磷酸化H2 AX灶可能显示出集落形成潜力的丧失。然而，结果表明，在一些肿瘤细胞系中，残留灶与放射敏感性之间没有密切的相关性，这些肿瘤细胞系显示内源性磷酸化H2 AX灶的高表达。此外，由X射线照射诱导的微核有磷酸化的H2 AX焦点，但磷酸化的ATM，磷酸化的DNA-PKcs和53 BP 1焦点不共定位。这些结果表明，DNA DSB可能不是微核产生或H2 AX磷酸化的直接原因。(227话）。
Ionizing radiation causes DNA double strand breaks (DSBs), which produce a chromosomal change with the modification of chromatin protein. The histone H2AX is phosphorylated, and phosphorylated H2AX makes a focus. The phosphorylated H2AX focus is regarded as recruiting mediators of repair factors of DNA DSBs. Although most of the initial phosphorylated H2AX foci disappear with the repair of DNA DSBs, a few foci remain, and whether these residual DSBs are correlated with radiosensitivity is not clear. Therefore, we examined the correlation between residual DSBs and cellular radiosensitivity after ionizing radiation. We found that half of the non-irradiated normal cells had a few phosphorylated H2AX foci constantly, and most of the cells irradiated with less than 1% of the colony-forming dose had phosphorylated H2AX foci even 5 days after irradiation. Some tumor cell lines had phosphorylated H2AX foci even under non-irradiated conditions. These results indicate that residual phosphorylated H2AX foci may show loss of colony-forming potential after irradiation in normal cell lines. However, results suggested that there was not a close correlation between residual foci and radiosensitivity in some tumor cell lines, which showed high expression of endogenous phosphorylated H2AX foci. Moreover, micronuclei induced by X-ray irradiation had phosphorylated H2AX foci, but phosphorylated ATM, phosphorylated DNA-PKcs, and 53BP1 foci were not co-localized. These results suggest that DNA DSBs may be not a direct cause of micronuclei generation or H2AX phosphorylation. (227 words).