Measurement of chromosomal instability and level of DNA damage in peripheral blood mononuclear cells of endometrial cancer patients.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2024-04-24 DOI:10.1093/mutage/geae003
Aleksandra Marković, Darko Grujičić, Marija Živković Radojević, Olivera Milošević-Djordjević
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Abstract

Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries. The aim of this study was to evaluate chromosomal instability and level of DNA damage in peripheral blood mononuclear cells (PBMCs) of newly diagnosed endometrial cancer patients in relation to health status (diagnosis), age, histological grade of cancer, residence, smoking, number of pregnancies, miscarriages, and abortions. The analyzed sample consisted of 60 individuals, 30 endometrial cancer patients with an average age of 64.37 ± 7.08, and 30 healthy control women with an average age of 60.23 ± 11.55. Chromosomal instability was evaluated by the cytokinesis-block micronucleus (CBMN) assay, and the level of DNA damage by the single-cell gel electrophoresis (comet) assay in PBMCs. The average frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) as well as nuclear buds (NBUDs) were significantly higher in cancer patients compared to controls (P < .0005). There was no difference in the nuclear division index (NDI) among the analyzed samples. The comet assay showed that the patients had a significantly increased genetic damage index (GDI) compared with controls (P < .0005). Using linear regression analysis, we found that health status (diagnosis) had the strongest influence on the MN frequency as well as GDI (P < .0005). Our results indicated that there is a high level of genetic damage in both the level of DNA and the level of chromosomes in the PBMCs of newly diagnosed patients with endometrial cancer, where the frequency and level of damage were significantly affected by health status, grade of cancer, residence, number of pregnancies, miscarriages, and abortions.

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测量子宫内膜癌患者外周血单核细胞的染色体不稳定性和 DNA 损伤水平。
子宫内膜癌是发达国家最常见的侵袭性妇科恶性肿瘤之一。本研究旨在评估新诊断的子宫内膜癌患者外周血单核细胞(PBMC)中染色体不稳定性和 DNA 损伤水平与健康状况(诊断)、年龄、癌症组织学分级、居住地、吸烟、怀孕次数、流产和堕胎的关系。分析样本由 60 人组成,其中 30 人为子宫内膜癌患者,平均年龄为(64.37 ± 7.08)岁;30 人为健康对照妇女,平均年龄为(60.23 ± 11.55)岁。染色体不稳定性通过细胞分裂阻滞微核(CBMN)检测法进行评估,DNA损伤水平通过单细胞凝胶电泳(彗星)检测法在PBMCs中进行评估。与对照组相比,癌症患者的微核(MNi)、核质桥(NPBs)和核芽(NBUDs)的平均频率明显更高(P < 0.0005)。分析样本的核分裂指数(NDI)没有差异。彗星试验显示,与对照组相比,患者的遗传损伤指数(GDI)明显升高(p < 0.0005)。通过线性回归分析,我们发现健康状况(诊断)对 MN 频率和 GDI 的影响最大(p < 0.0005)。我们的研究结果表明,新诊断的子宫内膜癌患者的 PBMC 中 DNA 水平和染色体水平均存在较高程度的遗传损伤,其损伤频率和损伤程度受健康状况、癌症等级、居住地、妊娠次数、流产次数和人工流产次数的显著影响。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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