Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition
Open accessAbstract
The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).
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The hypothesis that BRCA mutation is associated with increased radio sensitivity was supported by experimental and clinical data.
“The hypothesis that BRCA mutation is associated with increased radio sensitivity was supported by experimental and clinical data [12-19].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [12]
BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation.
“Several studies suggest that BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation [5-12].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [12]
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Cites
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“The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay.”
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“…recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2…”
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“Although recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks a…”
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“For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy 60Co g-rays at a high dose rate or low dose rate.”
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“[139] have Table 1 The radiosensitivity level of breast cancer patients, BRCA1/2 mutation carriers and breast cancer patients with radiotherapy complication, using micronucleus assay (Continued)”
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Self-citationDNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers
Kotsopoulos, J., Chen, Z., Vallis, K. A., Poll, A., Ainsworth, P., & Narod, S. A. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603528 · Cited by 46 · see citing works
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“Some investigators found a high sensitivity and a reduced repair capacity in peripheral blood cells from breast cancer patients when exposed to X-rays, gamma and UV light, as evaluated by the determination of chromosome aberrations [15,17,18] micronuclei (MN) [2,4,5,14,16], and DNA fragmentation by means of the comet…”
BackgroundMethodResultChromosomal mutagen sensitivity associated with mutations in BRCA genes
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ResultA standardized G2-assay for the prediction of individual radiosensitivity
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Self-citationPrognostic role of adjuvant radiotherapy in triple‐negative breast cancer: A historical cohort study
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“In a number of independent studies, enhanced in vitro chromosomal radiosensitivity (CRS) has been demonstrated in a significant number of breast cancer patients (3-8).”
Langhe, S. D., Meerleer, G. D., Ruyck, K. D., Ost, P., Fonteyne, V., Neve, W. D., & Thierens, H. (2014) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2014.04.005 · Cited by 37 · see citing works
“This is plausible as it is hypothesized that there is an overlap between polymorphisms associated with breast cancer and radiosensitivity [27].”
BackgroundSelf-citationThe Cell Cycle G2/M Block Is an Indicator of Cellular Radiosensitivity
Liu, C., Nie, J., Wang, R., & Mao, W. (2019) · Dose-Response · doi:10.1177/1559325819891008 · Cited by 33 · see citing works
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“Several of these studies have revealed impaired DNA repair capacity in peripheral blood mononuclear cells (PBMCs), exposed in vitro to ionizing radiation (IR) or UV from breast cancer patients, as evaluated by the chromosome aberration assay [8–10] as well as by the micronucleus test [11–13].”
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Mozdarani, H. (2012) · Genes · doi:10.3390/genes3010090 · Cited by 31 · see citing works
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Mechanisms of the formation of radiation-induced chromosomal aberrations
Bryant, P. E., Riches, A., & Terry, S. Y. A. (2010) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2010.03.016 · Cited by 29 · see citing works
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Baeyens, A. (2004) · Mutagenesis · doi:10.1093/mutage/geh029 · Cited by 26 · see citing works
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Gutiérrez‐Enríquez, S., y Cajal, T. R., Alonso, C., Corral, A., Carrasco, P., Cornet, M., Sanz, J., Ribas, M., Baiget, M., & Dı́ez, O. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-1017-6 · Cited by 24 · see citing works
T lymphocytes to predict radiation-induced late effects in normal tissues
Brengues, M., Lapierre, A., Bourgier, C., Pèlegrin, A., Özşahin, M., & Azria, D. (2016) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2017.1271715 · Cited by 24 · see citing works
Docherty, Z., Georgiou, A. L., Langman, C., Kesterton, I., Rose, S., Camplejohn, R. S., Ball, J., Barwell, J., Gilchrist, R., Pangon, L., et al. (2006) · International Journal of Radiation Biology · doi:10.1080/09553000600932968 · Cited by 24 · see citing works
“Other previous studies used unmatched control groups, (Baeyens et al. 2002, 2005, Buchholz & Wu 2001), or controls with a lower mean and range of ages than the breast cancer patients (Baeyens et al. 2002, 2005) or surgical outpatients without malignancy (Riches et al. 2001).”
BackgroundMethodResultInfluentialDiagnosis of Fanconi Anaemia by ionising radiation- or mitomycin C-induced micronuclei
Francies, F. Z., Wainwright, R., Poole, J., Leeneer, K. D., Coene, I., Wieme, G., Poirel, H. A., Brichard, B., Vermeulen, S., Vral, A., et al. (2017) · DNA repair · doi:10.1016/j.dnarep.2017.11.001 · Cited by 23 · see citing works
Self-citationChromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?
Ruyck, K. D., de Gelder, V., Eijkeren, M. V., Boterberg, T., Neve, W. D., Vral, A., & Thierens, H. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604345 · Cited by 23 · see citing works
Self-citationVandevoorde, C., Depuydt, J., Veldeman, L., Neve, W. D., Sebastià, N., Wieme, G., Baert, A., Langhe, S. D., Philippé, J., Thierens, H., et al. (2016) · International Journal of Radiation Biology · doi:10.1080/09553002.2016.1230238 · Cited by 23 · see citing works
Self-citationTrenz, K., Schütz, P., & Speit, G. (2005) · Mutagenesis · doi:10.1093/mutage/gei018 · Cited by 22 · see citing works
Wang, X., Wu, X., Liang, Z., Huang, Y., Fenech, M. F., & Xue, J. (2005) · Mutagenesis · doi:10.1093/mutage/gei069 · Cited by 22 · see citing works
Luxton, J. J., McKenna, M. J., Lewis, A. M., Taylor, L. E., Jhavar, S. G., Swanson, G. P., & Bailey, S. M. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11030188 · Cited by 21 · see citing works
Shahidi, M., Mozdarani, H., & Mueller, W.-U. (2010) · Europe PMC (PubMed Central) · Cited by 20 · see citing works
Meade, A. D., Maguire, A., Bryant, J., Cullen, D., Medipally, D., White, L., McClean, B., Shields, L., Armstrong, J., Dunne, M., et al. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1451006 · Cited by 20 · see citing works
In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency
Mahmoodi, M., Abolhassani, H., Mozdarani, H., Rezaei, N., Azizi, G., Yazdani, R., Farzanfar, F., Rafiemanesh, H., Mohagheghi, M. A., Divsalar, K., et al. (2018) · Central European Journal of Immunology · doi:10.5114/ceji.2018.77385 · Cited by 20 · see citing works
Howe, O. L., O’Malley, K., Lavin, M. F., Gardner, R. A., Seymour, C. B., Lyng, F. M., Mulvin, D., Quinlan, D. M., & Mothersill, C. E. (2005) · Radiation Research · doi:10.1667/rr3454.1 · Cited by 20 · see citing works
Howe, O. L., O'Sullivan, J. N., Nolan, B., Vaughan, J. E., Gorman, S., Clarke, C., McClean, B., & Lyng, F. M. (2009) · Radiation Research · doi:10.1667/rr1579.1 · Cited by 19 · see citing works
Scott, D., Spreadborough, A. R., & Roberts, S. A. (2003) · International Journal of Radiation Biology · doi:10.1080/0955300031000150602 · Cited by 19 · see citing works
Comparison of bleomycin and radiation in the G2 assay of chromatid breaks
Adema, A. D., Cloos, J. J., Verheijen, R. H. M., Braakhuis, B. J. M., & Bryant, P. E. (2003) · International Journal of Radiation Biology · doi:10.1080/09553000310001596968 · Cited by 17 · see citing works
The potential role of G2- but not of G0-radiosensitivity for predisposition of prostate cancer
Borgmann, K., Raabe, A., Reuther, S., Szymczak, S., Schlomm, T., Hendrik Isbarn, A., Gomolka, M., Busjahn, A., von Bonin, M., Ziegler, A., et al. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.04.018 · Cited by 16 · see citing works
“It is already known that G0- and G2-radiosensitivity are not correlated [4,13,23].”
BackgroundResultCullen, D., Bryant, J., Maguire, A., Medipally, D., McClean, B., Shields, L., Noone, E., Bradshaw, S., Finn, M. A., Dunne, M., et al. (2020) · Translational Biophotonics · doi:10.1002/tbio.201900035 · Cited by 16 · see citing works
“Although it would have been more relevant to carry out the G2 assay on PBMC cultures for this study as PBMC cultures were used for the γH2AX assay and the Raman assay, it was decided to use whole blood cultures as these are routinely used for the G2 assay (43-49) but also because our previous study establishing the ra…”
MethodVarga, D., Michel, I., Patiño‐García, B., Paiss, T., Vogel, W., & Maier, C. (2005) · Cytogenetic and Genome Research · doi:10.1159/000085668 · Cited by 16 · see citing works
Imano, N., Nishibuchi, I., Kawabata, E., Kinugasa, Y., Shi, L., Sakai, C., Ishida, M., Sakane, H., Akita, T., Ishida, T., et al. (2020) · Radiation Research · doi:10.1667/rade-20-00234.1 · Cited by 15 · see citing works
Chromosomal radiosensitivity of breast cancer with a mutation
Baeyens, A., Claes, K., Willems, P. H. G. M., DERUYCK, K., Thierens, H. M., & Vral, A. (2005) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2005.04.017 · Cited by 15 · see citing works
Self-citationDhillon, V. S., Yeoh, E. K., Salisbury, C., Butters, J., Matteo, A. D., Olver, I., & Fenech, M. F. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22240 · Cited by 14 · see citing works
“Furthermore, this assay also measures DNA damage repair defects associated with heritable cancer proneness (Rothfuss et al., 2000; Baeyens et al., 2002; Fenech et al., 2016).”
BackgroundBonassi, S., & Fenech, M. F. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788013604-00038 · Cited by 14 · see citing works
Vandersickel, V., Mancini, M., Marras, E., Willems, P., Slabbert, J. P., Philippé, J., Deschepper, E., Thierens, H., Perletti, G., & Vral, A. (2010) · International Journal of Radiation Biology · doi:10.3109/09553000903419940 · Cited by 14 · see citing works
Self-citationShovman, O., Riches, A., Adamson, D. J. A., & Bryant, P. E. (2008) · Mutagenesis · doi:10.1093/mutage/gen009 · Cited by 14 · see citing works
Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer
Abdollahi, E., Mozdarani, H., & Alizadeh, B. Z. (2023) · Breast Cancer · doi:10.1007/s12282-023-01463-4 · Cited by 13 · see citing works
“An increase in CA after irradiation has been shown in about 40% of BC patients, but only in about 10% of healthy subjects [9, 10].”
BackgroundAbdel‐Rahman, S. Z., & El‐Zein, R. A. (2011) · Biomarkers · doi:10.3109/1354750x.2011.577237 · Cited by 13 · see citing works
Radiosensitivity in patients suffering from chronic kidney disease
Rodríguez‐Ribera, L., Corredor, Z., Sandoval, S. B., Coll, E., Silva, I., Díaz, J. M., Ballarín, J., Marcos, R., & Pastor, S. (2014) · International Journal of Radiation Biology · doi:10.3109/09553002.2015.959670 · Cited by 13 · see citing works
Terry, S. Y. A., Riches, A., & Bryant, P. E. (2009) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2009.01.003 · Cited by 12 · see citing works
Mayo, T., Haderlein, M., Schuster, B., Wiesmüller, A., Hummel, C., Bachl, M., Schmidt, M., Fietkau, R., & Distel, L. V. (2019) · Radiation Oncology · doi:10.1186/s13014-019-1444-4 · Cited by 12 · see citing works
Wilding, C. S., Curwen, G. B., Tawn, E. J., Sheng, X., Winther, J. F., Chakraborty, R., & Boice, J. D. (2006) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20274 · Cited by 12 · see citing works
Wilson, P. F., Nagasawa, H., Fitzek, M. M., Little, J. B., & Bedford, J. S. (2009) · Radiation Research · doi:10.1667/rr1943.1 · Cited by 12 · see citing works
The cytokinesis-block micronucleus assay for cryopreserved whole blood
Beyls, E., Baeyens, A., & Vral, A. (2021) · International Journal of Radiation Biology · doi:10.1080/09553002.2021.1941378 · Cited by 11 · see citing works
“The cytokinesis-block micronucleus assay has proven to be a reliable test for radiosensitivity assessment in cancer patients or patients with a genetic defect in the DNA repair pathway (Baeyens et al. 2002; Mohseni-Meybodi et al. 2007; Claes et al. 2013; Francies et al. 2018).”
BackgroundSelf-citationSchmitz, S., Brzozowska, K., Pinkawa, M., Eble, M. J., & Kriehuber, R. (2013) · Radiation Research · doi:10.1667/rr3239.1 · Cited by 11 · see citing works
Bakhtari, N., Mozdarani, H., Salimi, M., & Omranipour, R. (2020) · Neoplasma · doi:10.4149/neo_2020_200225n185 · Cited by 10 · see citing works
A model of survivorship in cancer genetic care
Jacobs, L. A., & Giarelli, E. (2004) · Seminars in Oncology Nursing · doi:10.1053/j.soncn.2004.04.006 · Cited by 10 · see citing works
Poggioli, T., Sterpone, S., Palma, S., Cozzi, R., & Testa, A. (2010) · Journal of Radiation Research · doi:10.1269/jrr.10052 · Cited by 10 · see citing works
In vitroradiosensitivity of peripheral blood lymphocytes in multiple sclerosis patients
Petcu, I., Savu, D., Thierens, H., Nagels, G., & Vral, A. (2006) · International Journal of Radiation Biology · doi:10.1080/09553000600932976 · Cited by 10 · see citing works
“…performed investigating the radiosensitivity of lymphocytes in cancer patients to obtain bio-markers for cancer predisposition or individual hypersensitive reactions to radio-therapeutic treatments (Andreassen et al. 2002, Baeyens et al. 2002, Borgmann et al. 2002, Scott 2004, Vral et al. 2004).”
BackgroundMethodSelf-citationHerd, O., Francies, F. Z., Kotzen, J., Smith, T., NXUMALO, Z., Muller, X., Slabbert, J. P., Vral, A., & Baeyens, A. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4504 · Cited by 10 · see citing works
Self-citationThe use of IL-2 cultures to measure chromosomal radiosensitivity in breast cancer patients
Baeyens, A. (2004) · Mutagenesis · doi:10.1093/mutage/geh063 · Cited by 10 · see citing works
Self-citationLow-Dose 3D Quantitative Vascular X-ray Imaging of the Breast
de Carvalho, P. M. (2014) · doi:10.70675/29a7a82azf1f3z4f27zae25zfca270ccc579 · Cited by 10 · see citing works
Zahnreich, S., Poplawski, A., Hartel, C., Eckhard, L. S., Galetzka, D., Hankeln, T., Löbrich, M., Marron, M., Mirsch, J., Ritter, S., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01338 · Cited by 9 · see citing works
“Moreover, these results point toward higher fractions of IR sensitive individuals among young adults with early-onset cancers (14, 26).”
ResultEffects of estradiol and progesterone on the variability of the micronucleus assay
Baeyens, A., Vandersickel, V., Thierens, H., Ridder, L. D., & Vral, A. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.05.013 · Cited by 9 · see citing works
Self-citationAbdollahi, E., & Mozdarani, H. (2023) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2023.104865 · Cited by 8 · see citing works
Cherednichenko, O., Pilyugina, A., & Nuraliev, S. (2021) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503434 · Cited by 8 · see citing works
Jian-Lin, L. O. U., Chen, Z., Jiang, W., He, J., Jin, L., Chen, S., Wei, Z., & Xu, S. (2008) · Biomedical and Environmental Sciences · doi:10.1016/s0895-3988(09)60009-x · Cited by 8 · see citing works
Hu, J. J., Hill, J. W., & Hu, J. J. (2009) · Cancer Management and Research · doi:10.2147/cmar.s4548 · Cited by 7 · see citing works
Chromosomal Radiosensitivity in Secondary‐Progressive Multiple Sclerosis Patients
Petcu, I., Savu, D., Vral, A., Thierens, H., Nagels, G., & Ridder, L. D. (2004) · International Journal of Radiation Biology · doi:10.1080/09553000400007664 · Cited by 7 · see citing works
“In these cancer patient studies no correlation was however found between G0 and G2 chromosomal radiosensitivity (Scott et al. 1999, Baeyens et al. 2002).”
BackgroundResultInfluentialSelf-citationKassem, T. Z., Wunderle, M., Kuhlmann, L., Ruebner, M., Huebner, H., Hoyer, J., Reis, A., Fasching, P. A., Beckmann, M. W., Hack, C. C., et al. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45080418 · Cited by 6 · see citing works
Nie, J., Shao, J., Guo, S., & Liu, X. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-87 · Cited by 6 · see citing works
- Authors
- Baeyens, A., Thierens, H., Claes, K., Poppe, B., Messiaen, L., De Ridder, L., & Vral, A.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Vral, A
- Venue
- British Journal of Cancer
- Published
- 2002-11-26
- Volume
- 87
- Issue
- 12
- Pages
- 1379-1385
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2376291
- OpenAlex
- W2073895085
- Cited by
- 136
- References
- 38
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Keywords
- chromosomal radiosensitivity, breast cancer, genetic susceptibility, family history (medicine), micronucleus test, chromatid breaks, lymphocytes, gamma irradiation, dose rate, young patients
- MeSH terms
- Adult, Aged, Breast Neoplasms, Chromosome Aberrations, Female, Gamma Rays, Humans, Lymphocytes, Middle Aged, Mutation, Radiation Tolerance, X-Rays, Micronucleus Tests, Resting Phase, Cell Cycle, G2 Phase, BRCA1 Protein, Genetic Predisposition to Disease, BRCA2 Protein
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