Buchynska L G, Brieieva O V
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2018 Mar;40(1):68-72.
The development of hormone-dependent cancers, including endometrial carcinomas, in great part may be mediated by the genotoxic effects of estrogen metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most prominent DNA-damaging properties. It is assumed that the individual sensitivity to the 4OHE2 may determine the predisposition to endometrial cancer (EС).
To analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to the 4OHE2 and to evaluate the repair efficiency of 4OHE2-induced DNA damage.
The study was performed on the PBLs of 53 EC patients and 20 healthy women. The level of DNA damage was measured using the comet assay and was expressed as % tail DNA. The DNA repair efficiency (%) was evaluated by determining the ratio between the amount of repaired DNA damage and the level of 4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2.
In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 ± 2.2% tail DNA) and lower DNA repair efficiency (34.0 ± 4.5%) was observed compared to PBLs of healthy women (22.3 ± 2.3% tail DNA and 48.8 ± 4.5%, respectively). PBLs of EC patients with deep tumor invasion of myometrium were characterized by more prominent decrease of DNA repair than those with less invasive tumor (< ½ of myometrium) (20.9 ± 7.8 and 43.7 ± 6.7%, respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs of EC patients with a family history of cancer compared to this parameter in patients with sporadic tumors (20.9±7.8 and 47.1 ± 5.5%, respectively).
The PBLs of EC patients are characterized by increased sensitivity to the genotoxic effect of 4OHE2 and reduced repair efficiency regarding 4OHE2-induced DNA damage. A lower level of DNA repair is observed in EC patients with deep tumor myometrial invasion and a family history of cancer.
包括子宫内膜癌在内的激素依赖性癌症的发生，很大程度上可能由雌激素代谢产物的基因毒性作用介导，其中4-羟基雌二醇（4OHE2）具有最显著的DNA损伤特性。据推测，个体对4OHE2的敏感性可能决定子宫内膜癌（EC）的易感性。
分析子宫内膜癌患者外周血淋巴细胞（PBLs）对4OHE2的敏感性，并评估4OHE2诱导的DNA损伤的修复效率。
对53例子宫内膜癌患者和20名健康女性的PBLs进行研究。使用彗星试验测量DNA损伤水平，并以尾DNA百分比表示。通过确定修复的DNA损伤量与PBLs与4OHE2孵育后出现的4OHE2诱导损伤水平之间的比率来评估DNA修复效率（%）。
与健康女性的PBLs（分别为22.3±2.3%尾DNA和48.8±4.5%）相比，子宫内膜癌患者的PBLs中观察到更高水平的4OHE2诱导的DNA损伤（32.
