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Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers
- Source :
- BREAST CANCER RESEARCH AND TREATMENT, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Adult
Cancer Research
In vitro radiation
endocrine system diseases
DNA damage
Mitomycin
Genes, BRCA2
Genes, BRCA1
Breast Neoplasms
Micronuclei
Biology
medicine.disease_cause
Loss of heterozygosity
03 medical and health sciences
0302 clinical medicine
Mitomycin C
medicine
Biomarkers, Tumor
Humans
Radiosensitivity
Lymphocytes
Allele
skin and connective tissue diseases
Nucleoplasmins
BRCA1 and BRCA2
Micronuclei, Chromosome-Defective
030304 developmental biology
0303 health sciences
Mutation
Cell Cycle
Cancer
Middle Aged
medicine.disease
Molecular biology
female genital diseases and pregnancy complications
3. Good health
Oncology
030220 oncology & carcinogenesis
Micronucleus test
Cancer research
Female
Subjects
Details
- ISSN :
- 15737217 and 01676806
- Volume :
- 127
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Breast cancer research and treatment
- Accession number :
- edsair.doi.dedup.....c525105943e00a39ad442695fe600763