Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Kopjar, Nevenka; Garaj‐Vrhovac, Vera; Milas, Ivan

doi:10.1002/tcm.1035

Cited by 51 publications

(30 citation statements)

References 52 publications

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“…4 In addition, the difference between the amount of drug needed to induce successful tumoricidal action and the amount needed to induce toxicity in the host is small and depends on individual characteristics. 8 Because radiation and most of the drugs applied in breast cancer treatment affect DNA, DNA damage must be considered as a plausible therapy side effect. 15 It has been reported that the comet assay, using peripheral blood lymphocytes, is sensitive enough to detect DNA damage as a result of the cancer treatments because lymphocytes are also affected by the treatments.…”

Section: Discussionmentioning

confidence: 99%

“…7 DNA damage caused by anti-neoplastic drugs and ionizing radiation includes nucleotide damage, breaking of hydrogen bonds between the two helices, single-strand breaks, double-strand breaks, appearance of apurinic or apyrimidinic sites, DNA protein cross-links, DNA-DNA interstrand crosslinks, DNA intrastrand cross-links, and generation of reactive oxygen species, which, in turn, cause more DNA damage. 2,8,9 DNA damage related to the exposure of cancer patients to therapy is frequently determined using peripheral blood lymphocytes as target cells. Lymphocytes have been proven to be good surrogate cells with which to investigate DNA damage because they are affected by agents used in cancer treatment and also are easy to obtain.…”

Section: A U T H O R P R O O Fmentioning

confidence: 99%

“…Lymphocytes have been proven to be good surrogate cells with which to investigate DNA damage because they are affected by agents used in cancer treatment and also are easy to obtain. 8,10 Diverse methodological approaches have been developed to assess the genotoxic damage. Among them, the comet assay (single-cell gel electrophoresis) is a simple method for measuring DNA integrity in individual cells.…”

Section: A U T H O R P R O O Fmentioning

confidence: 99%

See 2 more Smart Citations

Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Ceballos

Funes

Massa

et al. 2014

J Environ Pathol Toxicol Oncol

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Radiotherapy and chemotherapy cause genotoxic side effects that are highly variable among patients. In this study, we evaluated DNA integrity using the comet assay in peripheral blood lymphocytes from breast cancer patients before ("pre-treatment patients"; n = 47) and after ("post-treatment patients"; n = 24) radiotherapy and/or chemotherapy treatment and from healthy donors (n = 15). Comet evaluation was made by visual (types 0-4) and digital (percentage of DNA remaining in the comet head = % head DNA) analysis. The association between the level of DNA damage and cancer prognostic factors was assessed. The treatments caused a significant increase in DNA damage registered by both visual (p < 0.001) and digital (p < 0.001) analyses. No significant associations between the level of DNA damage in pre-treatment patients and cancer prognostic factors were found. A significant correlation between the comet results from each patient before and after treatment (r = 0.64, p = 0.001) was observed. The % head DNA in post-treatment samples from patients with a high level of DNA damage before treatment (30.3 ± 3.1%, p < 0.01) was lower than in post-treatment samples from patients with a low-to-medium level of DNA damage before therapy (49.2 ± 4.4%). These results support the usefulness of the comet assay as a sensitive technique to evaluate basal DNA status and DNA damage caused by cancer treatments. The comet assay could contribute to treatment decisions, especially by taking into account the patient's basal DNA damage before therapy.

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Section: Discussionmentioning

confidence: 99%

Section: A U T H O R P R O O Fmentioning

confidence: 99%

Section: A U T H O R P R O O Fmentioning

confidence: 99%

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Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Ceballos

Funes

Massa

et al. 2014

J Environ Pathol Toxicol Oncol

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“…A key challenge in RT is to maximize radiation doses to cancer cells while minimizing damage to the surrounding non-target healthy tissue. Recent literature in the field of clinical oncology and RT still does not explain sufficiently the question of damages to non-target cells and tissues after chemo-radiation treatment [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic Analysis on the Yields of Chromosomal Aberrations Induced by the Scattered Doses of γ-Radiation

Kadam¹,

Shyama²

2016

J Nucl Med Radiat Ther

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The present study is undertaken to know the radiation dose-response of chromosomes in the non-target cells, viz. peripheral blood lymphocytes of cancer patients in a context of partial body irradiation. The genotoxic effect of γ-radiation was studied in Head and Neck Squamous Cell Carcinoma (HNSCC) patients exposed to various cumulative doses of 60 Co gamma rays during radiotherapy (RT). These patients (P 1 to P 10 ) were irradiated for a period of six weeks with a daily fraction of 2 Gy, consecutively for 5 days in every week. The clastogenic effects of radiation in these patients were analysed on every weekend employing chromosomal aberration (CA) assay. Radiosensitivity of these patients were analysed by employing linear regression analysis of the CAs induced by irradiation. Genetic damage observed in all patients on a weekly basis were recorded and analysed at the individual level in comparison with their own pre-therapy baseline data, employing student's t-test. Dicentrics, centric rings and chromatid breaks were observed as the major kinds of CAs. The total CAs observed were analyzed using two way ANOVA, showed significant (P<0.001) intra and inter-individual variations of the genotoxic effects. Further, a dose dependent increase of cytogenetic damage was observed in the non-target cells viz. lymphocytes. Further, cytogenetic studies in peripheral lymphocytes following gamma radiotherapy of tumors may help to understand the optimum/precise dose of radiation to be employed for RT, may also be useful to predict dosimetry and the possible secondary tumors in irradiated HNSCC patients.

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“…Jelentősége a sejtminták csökkentett számának a követelményén alapszik, képes számokban kifejezni a DNS-károsodást a nem proliferáló sejtekben [2,3].…”

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Use of comet assay for the risk assessment of oil- and chemical-industry workers

et al. 2014

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Bevezetés: A comet assay a DNS száltöréseinek kimutatására alkalmas fl uoreszcens mikroszkópos módszer. Jelentősége az alacsony sejtszámú mintáknál mutatkozik, képes számokban kifejezni a DNS-károsodást a nem proliferáltatható sejtekben. Célkitűzés: Genotoxikus, illetve oxidatív DNS-károsodásokat mértünk foglalkozásuk során benzollal, policiklusos aromás szénhidrogénekkel, illetve sztirollal exponált csoportokban. Célunk volt annak megvizsgálása, hogy a módszer használható-e genotoxikológiai monitorhatás markereként. Módszer: A comet assay alaplépései mellett az enzimkezelt mintát formamido-pirimidin-DNS glikoláz restrikciós enzimmel kezeljük, ami az oxidatív DNS-károsodás mértékére utal. Eredmények: A kezeletlen (genotoxikus DNS-károsodás) és a kezelt (oxidatív DNS-károsodás) minták esetében emelkedés volt tapasztalható a csóvahosszokat illetően minden csoporton belül a kontrollhoz képest. Követ-keztetések: Megállapítható, hogy a környezeti (munkahelyi) expozíció valószínűsíthető a vizsgált csoportokban. A comet assay kitűnő hatásmarker, illetve kiegészítő módszer lehet egy monitorrendszerben, amelynek adatai tájékoztatást adhatnak a munkahelyeken emelkedett genotoxikus hatások jelenlétéről vagy hiányáról. Orv. Hetil., 2014, 155(47), 1872-1875. Kulcsszavak: comet assay, foglalkozási expozíció, géntoxikológiai monitor, hatásmarker Use of comet assay for the risk assessment of oil-and chemical-industry workersIntroduction: The comet assay is a fl uorescent microscopic method that is able to detect DNA strand-breaks even in non-proliferative cells in samples with low cell counts. Aim: The aim of the authors was to measure genotoxic DNA damage and assess oxidative DNA damage caused by occupational exposure in groups exposed to benzene, polycyclic aromatic carbohydrates and styrene at the workplace in order to clarify whether the comet assay can be used as an effect marker tool in genotoxicology monitoring. Method: In addition to the basic steps of the comet assay, one sample was treated with formamido-pirimidine-DNA-glycolase restriction-enzyme that measures oxidative DNA damage. Results: An increase was observed in tail moments in each group of untreated and Fpg-treated samples compared to the control. Conclusions: It can be concluded that occupational exposure can be detected with the method. The comet assay may prove to be an excellent effect marker and a supplementary technique for monitoring the presence or absence of genotoxic effects.

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Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Cited by 51 publications

References 52 publications

Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Cytogenetic Analysis on the Yields of Chromosomal Aberrations Induced by the Scattered Doses of γ-Radiation

Use of comet assay for the risk assessment of oil- and chemical-industry workers

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