Scoring variability of micronuclei in binucleated human lymphocytes in a case-control study

Patiño-García, B; Hoegel, Josef; Varga, Dominic; Hoehne, Maren; I, Michel; Jainta, Silke; Kreienberg, R.; Maier, Christiane; Vogel, Walther

doi:10.1093/mutage/gel018

Cited by 32 publications

(15 citation statements)

References 16 publications

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“…This could not be related to a change in experimental conditions or to reported sources of MN variability such as storage time of the blood samples [37,38] and differences between scorers [39]. To reduce the inter-test variability, a direct comparison of cases with concurrent controls and/or automated counting by image analysis has been suggested [7,32].…”

Section: Discussionmentioning

confidence: 99%

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

Gutiérrez‐Enríquez

Cajal

Alonso

et al. 2010

Breast Cancer Res Treat

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BRCA1 and BRCA2 genes are essential in preserving the integrity of genome, and it is not unambiguously clear whether the heterozygosity status may affect BRCA1 or BRCA2 functions. This may have implications for the clinical management of BRCA1 and BRCA2 mutation carriers both in breast cancer (BC) screening modality and in cancer treatment based on DNA-damaging or DNA-repair-inhibiting drugs. We investigated whether lymphocytes carrying BRCA1 or BRCA2 mutations displayed an increased sensitivity to radiation or mitomycin C (MMC) in vitro treatments. Peripheral blood from 21 BRCA1 mutation carriers (12 with BC and 9 healthy), 24 BRCA2 carriers (13 with BC and 11 healthy), 15 familial BC patients without detected mutation in BRCA1 or BRCA2 and 16 controls without familial history of cancer (5 with BC and 11 healthy) were irradiated or treated with MMC. Chromosomal damage was measured using the cytokinesis-block micronucleus assay. We evaluated micronuclei (MN) and nucleoplasmic bridges (NPBs). The BRCA2 mutation carriers and familial BC patients without detected mutation in BRCA1 or BRCA2 showed less basal NPB than BRCA1 carriers and controls. The BRCA1 (+/-) or BRCA2 (+/-) lymphocytes did not have increased frequencies of MN or NPB after irradiation. In contrast, BRCA2 (+/-) lymphocytes presented higher levels of MN after MMC exposure than BRCA1 carriers and controls. The monoallelic BRCA1 or BRCA2 pathogenic mutations seem not to be associated with an enhanced radiosensitivity. The mutation of one BRCA2 allele conferred an increased sensitivity to MMC, presumably because of the role of this gene in the repair of MMC-induced DNA damage. This finding indicates that the MMC-induced MN analysis could be useful in identifying functional deficiencies of BRCA2 or genes related to BRCA2. Since MMC can be used as an anti-cancer drug, these data may be relevant for the management and follow-up of BRCA2 mutation carriers.

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Section: Discussionmentioning

confidence: 99%

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

Gutiérrez‐Enríquez

Cajal

Alonso

et al. 2010

Breast Cancer Res Treat

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“…Clumps of cells with obscured nuclear or cytoplasmic boundaries and overlapping of cells were avoided and separated or cells lying singly were preferred for counting of MNC. Criteria for MNC were followed as mentioned by Garcia et al [25]. Cells with double or multiple MN were given a score of 1.…”

Section: Methodsmentioning

confidence: 99%

Micronucleus in Cervical Intraepithelial Lesions and Carcinoma

Samanta¹,

Dey

Nijhawan

2010

Acta Cytologica

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Aims and Objectives: To score and compare micronucleus (MN) in the whole spectrum of cervical lesions including normal, inflammatory, abnormal squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and invasive cancer (IC) and to evaluate the role of MN as a biomarker in different pre-neoplastic and neoplastic lesions. Materials and Methods: A total of 224 slides, comprised of normal (40), inflammatory (40), ASC-US (30), LSIL (38), HSIL (30) and IC (46), were studied. All the cases of HSIL, IC and ASC-US had histopathology. The LSIL, normal and inflammatory smears were again reviewed by 2 experienced cytopathologists independently. Two observers separately and independently counted the number of micronucleated cells per 1,000 of epithelial cells in oil immersion magnification (×100 objective) which was expressed as MN score per 1,000 cells. Results: The mean MN scores ± SD in normal, inflammatory, ASC-US, LSIL, HSIL and IC cases of cervical lesions were 1.02 ± 1.59, 0.4250 ± 0.71208, 2.87 ± 2.21, 4.7368 ± 5.62179, 21.30 ± 17.18 and 18.50 ± 9.54, respectively. MN scores of IC and HSIL were significantly high compared to the normal (p < 0.000), the inflammatory (p < 0.000), the ASC-US (p < 0.000) and to the LSIL (p < 0.000) group (analysis of variance test). LSIL showed significant difference with the normal (p = 0.043), the inflammatory (p = 0.019), the HSIL (p < 0.000) and the IC (p < 0.000) group but not with the ASC-US (p = 0.342) group. Conclusions: MN scoring on the epithelial cells of cervix could be used as a biomarker in cancer screening. This is an easy, simple, reliable, reproducible and objective test which can be performed on routinely stained smears.

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“…Micronucleus assay in human peripheral lymphocytes usually used to assess chromosomal damage that caused by exposure to different environmental, occupational or lifestyle factors and for in vitro genotoxicity testing (Patino-Garcia et al 2006). Micronuclei (MN) are derived from chromosome fragments that arised from asymmetrical structural aberrations or represent whole chromosomes that are not incorporated into the nucleus during cell division.…”

Section: Introductionmentioning

confidence: 99%

Automated Detection of Binucleated Cell and Micronuclei using CellProfiler 2.0 Software

Ramadhani

Purnami

2013

HAYATI Journal of Biosciences

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Micronucleus assay in human peripheral lymphocytes usually used to assess chromosomal damage. Manual scoring of micronuclei can be time consuming and large numbers of binucleated cells have to be analyzed to obtain statistically relevant data. Automation of the micronuclei analysis using image processing analysis software can provide a faster and more reliable analysis of micronucleus assay. Here the used of CellProfiler an open access cell image analysis software for automatic detection of binucleated cells and micronuclei were reported. We aimed to know whether there was a significant difference in the number of binucleated cells and micronuclei that obtained by manual and CellProfiler counting. Wilcoxon Rank test was used for statistical analysis to test H 0 hypothesis that there was no significant difference in the number of binucleated cells and micronuclei that obtained by manual and CellProfiler counting. We analyzed 135 images for both manual and CellProfiler counting. Our results showed that there was no significant difference between manual and CellProfiler counting for binucleated cells (P = 0.851) and for micronuclei (P = 0.917). In conclusion, the binucleated cells and micronuclei counting using CellProfiler were comparable but not better than manual counting.

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Scoring variability of micronuclei in binucleated human lymphocytes in a case-control study

Cited by 32 publications

References 16 publications

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers

Micronucleus in Cervical Intraepithelial Lesions and Carcinoma

Automated Detection of Binucleated Cell and Micronuclei using CellProfiler 2.0 Software

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