scholarly journals DNA DAMAGE IN TUMOR CELLS AND PERIPHERAL BLOOD LYMPHOCYTES OF ENDOMETRIAL CANCER PATIENTS ASSESSED BY THE COMET ASSAY

2017 ◽  
Vol 39 (4) ◽  
pp. 299-303 ◽  
Author(s):  
L G Buchynska ◽  
O V Brieieva ◽  
N P Iurchenko ◽  
V V Protsenko ◽  
S V Nespryadko

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.

2018 ◽  
Vol 40 (1) ◽  
pp. 68-72 ◽  
Author(s):  
L G Buchynska ◽  
O V Brieieva

Background: 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). Aim: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.


2009 ◽  
Vol 18 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Ersilia Lucenteforte ◽  
Renato Talamini ◽  
Maurizio Montella ◽  
Luigino Dal Maso ◽  
Claudio Pelucchi ◽  
...  

2017 ◽  
Vol 108 ◽  
pp. S44
Author(s):  
Judith Beatriz Pupo Balboa ◽  
Nayade Pereira Roche ◽  
Marta Sonia Robaina Castellanos ◽  
Reinaldo Gutiérrez Gutiérrez ◽  
Anamarys Pandolfi Blanco ◽  
...  

2015 ◽  
Vol 66 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Fulya Dilek Gökalp Muranli ◽  
Martin Kanev ◽  
Kezban Ozdemir

Abstract The aim of this study was to evaluate the genetic damage in human peripheral blood lymphocytes following 24 and 48- hour exposure to a commercial diazinon formulation Basudin 60EM® at concentrations between 0.01 and 40 μg mL-1. For this purpose we used the micronucleus (MN), fluorescence in situ hybridization (FISH), and alkaline single cell gel electrophoresis (comet) assay. Diazinon significantly increased the frequency of micronucleated cells compared to control. Forty-eight-hour exposure increased this frequency even at lower concentrations (0.01-10 μg mL-1). The FISH results revealed aneugenic effects at 10 μg mL-1. The comet assay also confirmed DNA damage at concentrations between 10 and 40 μg mL-1. Our findings have confirmed the genotoxic potential of diazinon and its cytotoxic effect on human lymphocytes. The increased DNA damage in our study raises concern about the current assessment of the health risk posed by this pesticide and calls for a high level of caution in agricultural and household use.


2010 ◽  
Vol 116 (3) ◽  
pp. 594-595 ◽  
Author(s):  
T. Dellinger ◽  
D. Chase ◽  
G. Stablein ◽  
J. Vu ◽  
Y. Huang ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17113-e17113
Author(s):  
Rohini Manda ◽  
Naga Praneeth Raja ◽  
Uday Shankar ◽  
Mark Dignan ◽  
Nagapavani Kandagari

e17113 Background: Data from the US Cancer Statistics Working Group shows that the age-adjusted incidence of endometrial cancer was 25.6/100,000, 2009-2013 for the US and 24.9/100,000 for the Commonwealth of Kentucky. However, for the Kentucky River Area Development District (KR) in the Appalachian region, the rate was higher at 34.2/100,000. This investigation was designed to explore epigenetic factors related to the elevated incidence of endometrial cancer in the KR region of Kentucky. Methods: With IRB approval, retrospective data on women with endometrial cancer were abstracted from tumor registry records for the period 2005-2015. Data including age at diagnosis, family history of cancer, smoking, diabetes and demographic characteristics were analyzed using SPSS. Results: Data on 41 cases of endometrial cancer from 2005-2015 were included in the analyses. The age range was 37-87 with mean age 62. Of the 41 cases, 19.5% (8/41) were under age 50 at diagnosis. 2 out of 8 (25%) had family history of Lynch syndrome associated malignancies. 9 (22.0%) had family history of cancer. No significant associations between smoking, age at diagnosis and diabetes were noted. Conclusions: There is an increased incidence of endometrial carcinoma in Appalachian Kentucky in general, and elevated rates in women under age 50 compared to statewide and US rates. We have shown from our previous research that there is a higher incidence of lynch syndrome among young patients with colon cancer in Appalachian Kentucky. Similar findings were observed with endometrial cancer from this analysis. Further evaluation and genetic testing for any association with Lynch syndrome in this age group is needed.


2015 ◽  
Vol 37 (4) ◽  
pp. 272-276 ◽  
Author(s):  
L G Buchynska ◽  
O Brieieva ◽  
K N Nekrasov ◽  
S V Nespryadko

Aim: To assess the expression of mismatch repair (MMR) proteins MSH2 and MLH1 and carry out microsatellite analysis in patients with endometrial cancer (EC) with regard to the family history of cancer. Materials and Methods: Morphological and immunohistochemical study was performed on tumor tissue samples of 49 EC patients. Microsatellite instability was determined using PCR with primers which flank microsatellite region BAT-26. Results: A tendency to a decreased expression of both MSH2 and MLH1 markers in a group of EC patients with a family history of cancer as compared with a group without aggregation of cancer in family history was observed (labeling index — LI — was 36.1 ± 8.1% and LI 20.7 ± 9.1% versus LI 48.0 ± 5.8% and 33.8 ± 5.8%, respectively). It was determined that the number of EC patients with tumors deficient by expression of MMR markers was reliably higher in a group of patients with a family history of cancer than in a group of patients without aggregation of cancer in fami ly history (р < 0.05). It was shown that in a group of EC patients with a family history of cancer, MMR-proficient tumors were detected in 38.5% of cases. Microsatellite instability was determined in 10.7% of EC patients including one patient with aggregation of Lynch-associated tumors in family history. Conclusion: Family history of cancer of EC patients is associated with malfunctioning of the MMR system as well as may be related to alternative molecular mechanisms.


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