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通过彗星试验评估子宫内膜癌患者肿瘤细胞和外周血淋巴细胞中的DNA损伤。

DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay.

作者信息

Buchynska L G, Brieieva O V, Iurchenko N P, Protsenko V V, Nespryadko S V

机构信息

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.

National Cancer Institute of MH of Ukraine, Kyiv 03022, Ukraine.

出版信息

Exp Oncol. 2017 Dec;39(4):299-303.

Abstract

UNLABELLED

To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood.

AIM

To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients.

MATERIALS AND METHODS

DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA).

RESULTS

It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions.

CONCLUSION

Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer.

摘要

未标记

迄今为止,基因组不稳定不仅被认为是肿瘤细胞的一个共同特征,也是癌症患者非恶性细胞的一个共同特征,包括外周血淋巴细胞(PBL)。肿瘤细胞和PBL中基因组不稳定之间的关联问题,以及其与肿瘤进展的关系仍知之甚少。

目的

根据子宫内膜癌(EC)患者的临床和形态学特征,评估其肿瘤细胞和PBL中的DNA损伤水平。

材料与方法

通过彗星试验评估106份EC患者的PBL样本和42份肿瘤细胞悬液样本中的DNA损伤。30名健康女性的PBL用作对照。DNA损伤水平以彗星尾中DNA的百分比(%尾DNA)表示。

结果

结果显示,EC患者PBL中的DNA损伤量比健康供体高2.2倍(分别为8.3±0.7%和3.7±0.4%尾DNA)(p<0.05)。在本研究中,未观察到子宫内膜肿瘤细胞和PBL中的DNA损伤水平之间存在关联(r=0.11;p>0.05)。肿瘤细胞和PBL中的DNA损伤量均与肿瘤分化程度以及肌层浸润深度无关,但取决于EC患者的体重指数(BMI):BMI值升高的患者中观察到高水平的损伤。此外,肿瘤细胞中的DNA损伤水平与癌症家族聚集有关,有癌症家族史的EC患者的子宫内膜细胞中的DNA损伤水平显著高于散发性肿瘤患者(分别为32.3±2.9%和22.8±1.8%尾DNA)(p<0.05)。还发现,PBL中DNA损伤水平高的女性患EC的风险比损伤水平低的女性更大(优势比为3.5)。

结论

基因组不稳定表现为EC患者肿瘤细胞和PBL中DNA损伤水平升高,与BMI和癌症家族史有关,并且可以反映患癌倾向。

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