Aggregatibacter actinomycetemcomitans infection causes DNA double-strand breaks in host cells
Aggregatibacter actinomycetemcomitans infection causes DNA double-strand breaks in host cells
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放线菌聚集菌感染导致宿主细胞 DNA 双链断裂
DOI：
10.1111/gtc.12570
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Yamaoka Yoshio
中科院分区：
文献类型：
--
作者：
Teshima Rie;Hanada Katsuhiro;Akada Junko;Kawano Kenji;Yamaoka Yoshio
牙周病是一种炎症性疾病，是由牙周病原体感染引起的。长期牙周病会增加口腔癌发生的风险。与其他3种消化道癌症相似，口腔癌的发生也需要多种基因组不稳定性;然而，4与基因组不稳定性积累相关的风险因素知之甚少。在这里，我们假设特定的牙周病原体可能会增加基因组不稳定性的风险。6因此，我们根据在宿主细胞中诱导DNA 7双链断裂（DSB）的能力筛选了几种牙周病原体。我们发现，放线杆菌8放线共生菌Y 4感染诱导DSB在宿主细胞中的形成。目的探讨感染A.伴随放线菌的细胞通过10个凋亡染色体断裂而发生凋亡，用半胱天冬酶抑制剂Z-VAD-FMK处理细胞。11. A.在Z-VAD-FMK存在下，观察到放线菌共生体的断裂，甚至12，表明这种断裂独立于13细胞凋亡而发生。这些结果表明，一些牙周病原体可以增加宿主细胞中14个基因组不稳定性的风险，从而增加致癌的风险。15
Periodontal disease, an inflammatory disease, is caused by infection with periodontal 2 pathogens. Long-term periodontal disease increases the risk of oral carcinogenesis. Similar to 3 other peptic cancers, oral carcinogenesis also requires multiple genome instabilities; however, 4 the risk factors related to the accumulation of genome instabilities are poorly understood. Here, 5 we hypothesized that specific periodontal pathogens may increase the risk of genome instability. 6 Accordingly, we screened several periodontal pathogens based on the ability to induce DNA 7 double-strand breaks (DSBs) in host cells. We found that Actinobacillus 8 actinomycetemcomitans Y4 infection induced DSB formation in host cells. To assess whether 9 DSB formation induced by infection with A. actinomycetemcomitans occurred through 10 apoptotic chromosome fragmentation, cells were treated with a caspase inhibitor, Z-VAD-FMK. 11 DSB accumulation induced by infection with A. actinomycetemcomitans was observed, even 12 in the presence of Z-VAD-FMK, suggesting that this breakage occurred independently of 13 apoptosis. These results suggested that some periodontal pathogens can increase the risk of 14 genome instabilities in host cells and subsequently increase the risk of carcinogenesis. 15