Cytokinesis Block Micronucleus Cytome (CBMN Cyt) Assay Biomarkers and Their Association With Radiation Sensitivity Phenotype in Prostate Cancer Cases and DNA Repair Gene hOGG1 (C1245G) Polymorphism. (27th September 2018)

• Record Type: Journal Article
• Authors: Dhillon, Varinderpal S.; Yeoh, Eric; Salisbury, Carolyn; Butters, Julie; Di Matteo, Addolorata; Olver, Ian; Fenech, Michael
• Is Part Of: Environmental and molecular mutagenesis. Volume 59:Number 9(2018)
• Page Start: 813
• Page End: 821
• Publication Date: 2018-09-27
• Subjects: prostate cancer -- micronucleus (MN) -- nucleoplasmic bridge (NPB) -- nuclear bud (NBud) -- DNA repair; Mutagenesis -- Periodicals; Molecular genetics -- Periodicals; Mutagenèse -- Périodiques; Mutagenèse chimique -- Périodiques; Mutation -- Périodiques; Maladies de l'environnement -- Périodiques; Génétique moléculaire -- Périodiques; 576.542
• DOI: 10.1002/em.22240
• Languages: English
• ISSNs: 0893-6692

Abstract

Abstract : Prostate cancer (PC) is commonly diagnosed cancer in men but only a few risk factors, such as family history, ethnicity, and age have been established. Chromosomal instability is another possible risk factor but this has not been adequately explained previously. In this study, we tested the hypotheses that peripheral blood lymphocytes (PBL) of PC patients have (1) an abnormally high level of chromosomal instability; (2) that they are hypersensitive to ionizing radiation‐induced DNA damage; and (3) that these phenotypes are affected by hOGG1 (C1245G) polymorphism. These experiments were performed using the cytokinesis‐block micronucleus Cytome (CBMN cyt) assay in PC cases and controls. We found that spontaneous or radiation‐induced (3G) micronucleus (MN) frequency is not significantly different between both groups. However, spontaneous frequency of nucleoplasmic bridges (NPBs) and radiation‐induced nuclear buds (NBuds) were significantly higher in patients vs. controls ( P < 0.0001; P = 0.0005, respectively). In addition, apoptosis and nuclear division index (NDI) was significantly higher in patients compared to controls after radiation treatment ( P = 0.006; P = 0.0002, respectively). Furthermore carriage of at least one G allele of hOGG1 (C1245G) polymorphism was associated with a significantly increased odds ratio (OR) to have a base‐line MN, NPB, or NBud frequency greater than medium level compared to homozygotes for C allele (OR:1.94, 1.77, 2.36, respectively, P = 0.02; 0.04, and 0.004, respectively). Our results support the hypotheses that those who develop PC have significantly higher level of genomic instability which is further increased in those who carry G allele of the hOGG1 (C1245G) polymorphism. Environ. Mol. Mutagen. 59:813–821, 2018. © 2018 Wiley Periodicals, Inc.