PMID- 22430981
OWN - NLM
STAT- MEDLINE
DCOM- 20120529
LR  - 20151119
IS  - 1098-2280 (Electronic)
IS  - 0893-6692 (Linking)
VI  - 53
IP  - 4
DP  - 2012 May
TI  - Folate deficiency is associated with the formation of complex nuclear anomalies 
      in the cytokinesis-block micronucleus cytome assay.
PG  - 311-23
LID - 10.1002/em.21688 [doi]
AB  - Chromosomal instability (CIN) is an important hallmark to oncogenesis and can be 
      diagnosed morphologically by the presence of nuclear anomalies such as 
      micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBuds). We have 
      identified additional nuclear anomalies formed under folate-deficient conditions, 
      defined as "fused" nuclei (FUS), "circular" nuclei (CIR), and "horse-shoe" nuclei 
      (HS) and investigated their suitability for inclusion as additional CIN 
      biomarkers in the lymphocyte cytokinesis-block micronucleus cytome (CBMN-Cyt) 
      assay. Although the morphological appearance of FUS, CIR, and HS suggested an 
      origin from multiple NPB in the fusion region between the two nuclei, the very 
      low frequency of dicentric chromosomes in metaphase spreads from these cultures 
      did not support this model. Fluorescence in situ hybridization (FISH) analysis of 
      cytokinesis-blocked binucleated (BN) cells with peptide nucleic acid probes for 
      telomeres and centromeres (PNA-FISH) revealed a high proportion of fusion regions 
      contained both centromeric and telomeric DNA. This suggests that folate 
      deficiency may disrupt the process of sister chromatid separation and chromosome 
      segregation during mitosis. It was concluded that the FUS, CIR, and HS 
      morphologies represent promising biomarkers of CIN that are sensitive to folate 
      deficiency, and further validation and investigation of the mechanisms 
      responsible for their formation is warranted.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Bull, Caroline F
AU  - Bull CF
AD  - CSIRO Food and Nutritional Sciences, Adelaide, South Australia.
FAU - Mayrhofer, Graham
AU  - Mayrhofer G
FAU - Zeegers, Dimphy
AU  - Zeegers D
FAU - Mun, Grace Low Kah
AU  - Mun GL
FAU - Hande, M Prakash
AU  - Hande MP
FAU - Fenech, Michael F
AU  - Fenech MF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20120319
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (Biomarkers)
RN  - 0 (Peptide Nucleic Acids)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - *Biomarkers
MH  - Cell Nucleus/*pathology
MH  - Chromosomal Instability/genetics/*physiology
MH  - Cytogenetic Analysis
MH  - Folic Acid Deficiency/*pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/pathology
MH  - Male
MH  - Micronucleus Tests
MH  - Peptide Nucleic Acids
EDAT- 2012/03/21 06:00
MHDA- 2012/05/30 06:00
CRDT- 2012/03/21 06:00
PHST- 2011/12/22 00:00 [received]
PHST- 2012/02/09 00:00 [accepted]
PHST- 2012/03/21 06:00 [entrez]
PHST- 2012/03/21 06:00 [pubmed]
PHST- 2012/05/30 06:00 [medline]
AID - 10.1002/em.21688 [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 2012 May;53(4):311-23. doi: 10.1002/em.21688. Epub 2012 Mar 
      19.