DNA Damage in Peripheral Blood Mononuclear Cells in Patients with Breast Cancer
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Keywords

breast cancer
DNA damage in peripheral blood mononuclear cells
comet method

How to Cite

Tsyrlina, E., Poroshina, T., Vasilev , D., Enalgieva, D., Krivorotko, P., & Bershtein, L. (2023). DNA Damage in Peripheral Blood Mononuclear Cells in Patients with Breast Cancer. Voprosy Onkologii, 69(4), 692–698. https://doi.org/10.37469/0507-3758-2023-69-4-692-698

Abstract

can differentiate indolent growth from aggressive growth and more accurately predict response to treatment.

Aim. To evaluate the degree of genotoxic DNA damage in peripheral blood mononuclear cells (PBMCs) in primary BC patients and to compare this indicator with clinical parameters.

Materials and methods. The degree of DNA damage in PBMCs was determined in 64 patients with primary T1-2N0-1M0 BC before treatment and 83 cancer-free patients as a comparison group using the COMET method.

Results. BC patients had a statistically significant increase in the degree of DNA damage in PBMCs. The median percentage of lymphocytes with COMET in BC patients was 26.0 (17.50; 34.50), and in the comparison group of the same age 9.0 (3.00; 16.00), p < 0.0001. Genotoxic manifestations were more pronounced in patients with favorable clinical signs of tumor process. There was a tendency to increase the percentage of comets in RE+RP+ neoplasms, in which the median percentage of comets was 28.0 (19.0; 36.0), while in the RE-RP- group it equaled to 20.5 (16.0; 28.0).

Conclusion. The degree of DNA damage in PBMCs in BC should be considered as an effect of general genotoxic shifts that led to the development of the tumor process, rather than a result of the influence of the breast neoplasm itself.

https://doi.org/10.37469/0507-3758-2023-69-4-692-698
pdf (Русский)

References

Waks AG, Winer EP. breast cancer treatment. JAMA;2019;321(3):288-300. doi:10.1001/jama.2018.19323.

Curtit E, Mansi L, Maisonnette-Escot Y, et al. Prognostic and predictive indicators in early-stage breast cancer and the role of genomic profiling: Focus on the Oncotype DX Breast Recurrence Score Assay. Eur J Surg Oncol. 2017;43(5):921-930. doi:10.1016/j.ejso.2016.11.016.

Jenkins S, Kachur ME, Rechache KM. Rare Breast Cancer Subtypes. Curr Oncol Rep. 2021;23(5):54. doi:10.1007/s11912-021-01048-4.

De Abreu FB, Schwartz GN, Wells WA, et al. Personalized therapy for breast cancer. Clin Genet. 2014;86(1):62-7. doi:10.1111/cge.12381.

Lian W, Liu C, Gu B, et al. The early prediction of pathological response to neoadjuvant chemotherapy and prognosis: comparison of PET Response Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer criteria in breast cancer. Nucl Med Commun. 2020;41(3):280-287. doi:10.1097/MNM.0000000000001145.

Burrell RA, McClelland SE, Endesfelder D, et al. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494(7438):492–6. doi:10.1038/nature11935.

Liao CL, Peng SF, Chen JC, et al. Ally l Isothiocyanate Induces DNA Damage and Impairs DNA Repair in Human Breast Cancer MCF-7 Cells. Anticancer Res. 2021;41(9):4343-4351. doi:10.21873/anticanres.15239.

Fikrová P, Stětina R, Hronek M, et al. Application of the comet assay method in clinical studies. Wien Klin Wochenschr. 2011;123(23-24):693-9. doi:10.1007/s00508-011-0066-0.

Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2′ -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009;27(2):120-139. doi:10.1080/10590500902885684.

Sykora P, Witt KL, Revanna P, et al Next generation high throughput DNA damage detection platform for genotoxic compound screening. Sci Rep. 2018;8(1):2771. doi:10.1038/s41598-018-20995-w.

Milic M, Frustaci A, Del Bufalo A, et al. DNA damage in non-communicable diseases: A clinical and epidemiological perspective. Mutat. Res. 2015;776:118–127. doi:10.1016/j.mrfmmm.2014.11.009.

Azqueta A, Ladeira C, Giovannelli L, et al. Application of the comet assay in human biomonitoring: An An hCOMET perspective Mutat Res Rev. Mutat Res. 2020;783:108288. doi:10.1016/j.mrrev.2019.108288.

Møller P, Stopper H, Collins AR, et al. Measurement of DNA damage with the comet assay in high-prevalence diseases: current status and future directions. Mutagenesis. 2020;35(1):5-18. doi:10.1093/mutage/gez018.

Galardi F, Oakman C, Truglia MC, et al. Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in early breast cancer patients. Breast. 2012;21(3):336-42. doi:10.1016/j.breast.2012.02.007.

Cortes-Gutierrez EI, Hernandez-Garza F, Garcia-Perez JO, et al. Evaluation of DNA single and double strand breaks in women with cervical neoplasia based on alkaline and neutral comet assay techniques. J Biomed Biotechnol. 2012;2012:1–7. doi:10.1155/2012/385245.

Shimabukuro F, Neto CF, Sanches JA, et al. DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin. Melanoma Res. 2011;21(2):99–105. doi:10.1097/CMR.0b013e3283426839.

Chovanec M, Svetlovska D, Miskovska V, et al. The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer . Oncotarget. 2016;7;16:75996-76005. doi:10.18632/oncotarget. 12515.

Hapakova N, Sestakova Z, Holickova A, et al. High endogenous DNA damage levels predict hematological toxicity in testicular germ cell tumor patients treated with first-line chemotherapy. Clin Genitourin Cancer. 2019;17(5):e1020-e1025. doi:10.1016/j.clgc.2019.06.004.

Wozniak K, Kolacinska A, Blasinska-Morawiec M, et al. The DNA-damaging potential of tamoxifen in breast cancer and normal cells. Arch Toxicol. 2007;81(7):519-27. doi:10.1007/s00204-007-0188-3.

Blasiak J, Arabski M, Krupa R, et al. Basal, oxidative and alkylative DNA damage, DNA repair efficacy and mutagen sensitivity in breast cancer. Mutat Res. 2004;554(1-2):139-48. doi:10.1016/j.mrfmmm.2004.04.001.

Synowiec E, Stefanska J, Morawiec Z, et al. Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res. 2008;648(1-2):65-72. doi:10.1016/j.mrfmmm.2008.09.014.

Kopjar N, Milas I, Garaj-Vrhovac V, et al. Alkaline comet assay study with breast cancer patients: evaluation of baseline and chemotherapy-induced DNA damage in non-target cells. Clin Exp Med. 2006;6(4):177-90. doi:10.1007/s10238-006-0113-8.

Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51-88. doi:10.1146/annurev.pharmtox.45.120403.095857.

Uriol E, Sierra M, Comendador MA. Long-term biomonitoring of breast cancer patients under adjuvant chemotherapy: the comet assay as a possible predictive factor. Mutagenesis. 2013;28(1):39-48. doi: 10.1093/mutage/ges050.

McKelvey-Martin VJ, Green MH, Schmezer P, et al. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res. 1993;288;1:47-63. doi:10.1016/0027-5107(93)90207-v.

Ciriello G, Gatza ML, Beck AH, et al. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell. 2015;163(2):506-19.doi:10.1016/j.cell.2015.09.033.

Santos RA, Teixeira AC, Mayorano MB, et al. Basal levels of DNA damage detected by micronuclei and comet assays in untreated breast cancer patients and healthy women. Clin Exp Med. 2010;10(2):87-92. doi:10.1007/s10238-009-0079-4.

Цырлина Е.В., Порошина Т.Е., Оганесян А.П., и др. Повреждение ДНК мононуклеарных клеток периферической крови, выявленное методом «комет», как возможный показатель чувствительности меланомы к иммунотерапии ниволумабом. Сибирский онкологический журнал. 2021;20(2):37–45 [Tsirlina EV, Poroshina TE, Oganesyan AP, et al. Peripheral blood mononuclear DNA damage identified by the “comet” method, as a possible indicator of sensitivity of melanoma to immunotherapy with nivolunab. Siberian Journal of Oncology. 2021;20(2):37–45 (In Russ.)]. doi:10.21294/1814-4861-2021-20-2-37-45.

Цырлина Е.В., Порошина Т.Е., Васильев Д.А. и др. Повреждение ДНК в мононуклеарных клетках периферической крови у пациентов c меланомой.//Сибирский онкологический журнал. 2022;3:33-41 [Tsyrlina EV, Poroshina TE, Vasiliev DA, et al. DNA damage in peripheral blood mononuclear cells in patients with melanoma. Siberian journal of oncology. 2022;21(3):33-41 (In Russ.)] doi:10.21294/1814-4861-2022-21-3-33-41.

Bonassi S, Ceppi M, Møller P, et al. DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death. Sci Rep. 2021;11:16793. doi:10.1038/s41598-021-95976-7.

Marino M, Gigliotti L, Møller P, et al. Impact of 12-month cryopreservation on endogenous DNA damage in whole blood and isolated mononuclear cells evaluated by the comet assay. Sci Rep. 2021;11(1):363). doi:10.1038/s41598-020-79670-8.

Берштейн Л.М. Гормональный канцерогенез. СПб. Наука, 2000, 199 с. ISBN 5-02-026132-7. [Berstein LM. Hormonal carcinogenesis. St. Petersburg: Nauka. 2000;199. ISBN 5-02-026132-7 (In Russ.)].

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