Bleomycin-induced DNA damage and its removal in lymphocytes of breast cancer patients studied by comet assay

Jałoszyński, Paweł; Kujawski, Maciej; Czub-Świerczek, Maria; Markowska, Janina; Szyfter, Krzysztof

doi:10.1016/s0921-8777(97)00046-3

Cited by 102 publications

(61 citation statements)

References 25 publications

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“…This was similar to that reported by Vaghef et al [32]. Although baseline levels of DNA damage are influenced by personal life-style factors, it is also well documented that some human cancer-prone syndromes have both an increased susceptibility toward DNA damaging agents and a decreased ability of cells to repair DNA damage induced by genotoxins [35]. Furthermore, a higher rate of cytogenetic damage in peripheral blood lymphocytes has been found in subjects affected by some kind of tumors and their relatives when compared with control groups.…”

Section: Discussionsupporting

confidence: 90%

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

Kopjar

Garaj‐Vrhovac

Milas

2001

Teratog Carcinog Mutagen

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The alkaline comet assay was employed to assess the pre-and post-treatment levels of in vivo DNA damage in peripheral blood leukocytes of cancer patients. During the study all patients were given antineoplastic drugs, mainly as polychemotherapy. To quantify the DNA damage, two different comet parameters were evaluated: the tail length and the tail moment. Our results indicate marked interindividual variations between baseline DNA damage in peripheral blood leukocytes recorded among cancer patients prior to the chemotherapy. After intravenous administration of various antineoplastic drugs, a significantly increased level of DNA damage in all cancer patients compared to their pre-treatment values was recorded The highest level of DNA damage was seen following administration of 5-fluorouracil, adriamycin, and cisplatin (FAP protocol). The results indicate that administration of antineoplastic drugs in standard protocols is accompanied by significant DNA damage in peripheral blood leukocytes. In order to diminish the potential risks of developing second neoplasms, a continuous biomonitoring of cancer patients after the ending of chemotherapy becomes important. Despite their limitations, present results confirm the usefulness of the alkaline comet assay as a sensitive biomarker of exposure that enables rapid and simple detection of primary DNA damage in peripheral blood leukocytes of cancer patients. Together with standard cytogenetic endpoints, the comet assay provides a powerful technique for the routine detection of critical DNA lesions produced after administration of antineoplastic drugs in the clinical settings. Teratogenesis Carcinog. Mutagen. 22:13-30, 2002.

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Section: Discussionsupporting

confidence: 90%

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

Kopjar

Garaj‐Vrhovac

Milas

2001

Teratog Carcinog Mutagen

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“…Each image was classified according to the intensity of the fluorescence in the comet tail and was given a value of 0, 1, 2, 3, or 4 (from undamaged class 0 to maximally damaged class 4), so that the total scores ranged between 0 and 400 arbitrary units (AU) (Figure 1). [8] …”

Section: Analysis Of Total Sperm Dna Damagementioning

confidence: 99%

Analysis of the correlation between sperm DNA integrity and conventional semen parameters in infertile men

Aydos¹,

Yükselten²,

Kaplan³

et al. 2015

Turkish Journal of Urology

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Objective: A male factor is responsible in approximately 30-40% of couples receiving infertility treatment. Routinely, such couples undergo semen analysis including parameters such as sperm count, motility and morphology. Generally, the analysis of sperm DNA damage, shown to have a significant clinical importance by many studies, is recognized as an advanced test that is not included in routine infertility tests. Intracytoplasmic sperm injection method, commonly employed in the current infertility treatment protocols, lowers the fertilization rate, however, fertilization can occur even with a damaged DNA which is known to pose a risk in the subsequent pregnancy period. The relation between sperm morphology and the degree of sperm DNA damage has not yet been understood clearly. In this study, we aimed to investigate the association between routine semen analysis and sperm DNA integrity assay, another advanced but costly method. Material and methods:The degree of DNA damage was compared with the results of semen analysis, based on the WHO criteria, in 399 male patients who received comet assay for sperm DNA integrity. The statistical correlation analyses were performed with Windows SPPS statistical package program.Results: Accordingly, the sperm DNA damage was found to be correlated with all 3 parameters (sperm count, forward motility, and morphology) examined by the semen analysis (p<0.001). Total sperm DNA Damage Count was 226, 216, and 210 arbitrary units in patients with a sperm count <15 mil/mL, forward moving motility <32%, and normal morphology <4%, respectively. The difference with the normal individuals was statistically significant (p<0.001). Conclusion:In light of the comet assay results, higher degree of sperm DNA damage is associated with significant impairment of all seminal parameters.

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“…Some investigators found a high sensitivity and a reduced repair capacity in peripheral blood lymphocytes from breast cancer patients when exposed to X-rays, gamma and UV light, as evaluated by the determination of chromosome aberrations (9)(10)(11) and by the micronucleus test (12). While Hsu et al (13), using bleomycin in a mutagenic test, did not find a significant difference between blood cells from breast cancer patients and healthy subjects in terms of number of chromatid breaks per cell, Jaloszynski et al (14) reported a high sensitivity and reduced repair capacity in peripheral blood cells from breast cancer patients using the comet assay. Rothfuss et al (15) reported a higher sensitivity to gamma radiation and oxygen peroxide in patients with BRCA1 mutation than in healthy subjects using the micronucleus assay but not when using the comet assay.…”

Section: Introductionmentioning

confidence: 98%

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

Nascimento

Silva

Oliveira

et al. 2001

Braz J Med Biol Res

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Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60 Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the doseresponse curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

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Bleomycin-induced DNA damage and its removal in lymphocytes of breast cancer patients studied by comet assay

Cited by 102 publications

References 25 publications

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

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

Analysis of the correlation between sperm DNA integrity and conventional semen parameters in infertile men

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

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