Majone Franca, Zamboni Daniela, Cozzi Franco, Montaldi Anna, Grypiotis Panagiotis, Luisetto Roberto, Favaro Maria, Tonello Marta, Ruffatti Amelia
Department of Biology, University of Padova, Italy.
Eur J Dermatol. 2006 May-Jun;16(3):258-61.
The clastogenic effects on DNA, proven by the presence of micronuclei (MN), and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in patients with systemic sclerosis (SSc). The frequency of micronucleated cells found in cultures of peripheral lymphocytes in patients was significantly higher than in the control group. The patient group with anti-centromere antibodies showed a significantly higher frequency of micronucleated cells than that observed in the patients with anti-topoisomerase I antibodies (4.22% versus 2.34%, p < 0.001). Moreover, we attempted to characterize MN for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase. It was found that the frequency of MN containing DNA fragments with 3'-OH free ends (unstable fragments) increased in SSc patients compared to that observed in the control group. Moreover, this increase was significantly higher in lymphocytes of the patients with anti-centromere antibodies than in those with anti-topoisomerase I antibodies (35% versus 20.08%, p < 0.001). Our results indicate that in SSc patients there is an interference in the protective cellular mechanisms, normally stabilizing DNA breaks.
通过微核（MN）的存在证明对DNA的致断裂效应，以及通常用于稳定DNA断裂的保护性细胞机制，在系统性硬化症（SSc）患者中进行了研究。患者外周淋巴细胞培养物中发现的微核细胞频率显著高于对照组。抗着丝粒抗体患者组的微核细胞频率显著高于抗拓扑异构酶I抗体患者组（4.22%对2.34%，p<0.001）。此外，我们试图通过使用末端脱氧核苷酸转移酶的地高辛配基-dUTP（DIG-dUTP）来表征微核中是否存在具有游离3'-OH末端的DNA片段。结果发现，与对照组相比，SSc患者中含有3'-OH游离末端DNA片段（不稳定片段）的微核频率增加。此外，抗着丝粒抗体患者淋巴细胞中的这种增加显著高于抗拓扑异构酶I抗体患者（35%对20.08%，p<0.001）。我们的结果表明，在SSc患者中，通常稳定DNA断裂的保护性细胞机制受到了干扰。
