PMID- 20407220
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20211020
IS  - 1424-859X (Electronic)
IS  - 1424-8581 (Print)
IS  - 1424-8581 (Linking)
VI  - 128
IP  - 1-3
DP  - 2010
TI  - Nuclear bud formation: a novel manifestation of Zidovudine genotoxicity.
PG  - 105-10
LID - 10.1159/000298794 [doi]
AB  - Normal diploid somatic mammalian cell division generates 2 daughter cells as a 
      result of a strict and well-controlled mitotic process. However, some defects 
      during the progression of that process could generate an unbalanced distribution 
      of chromosomes, aneuploidy and eventually, a malignant phenotype. Previous 
      observations using a transgenic mouse model with diminished DNA repair capacity 
      revealed the presence of nuclear buds (NBs) induced in vitro by the nucleoside 
      analog zidovudine (Retrovir(R), 3'-azido-3'-deoxythymidine, AZT). Here we used 
      bone marrow mesenchymal cells, taken from mice with the Xpa(-/-)Trp53(+/-) 
      genotype, that were cultured and exposed to 0 and 100 muM AZT for 24 hours. Fixed 
      and denatured cells were processed by fluorescence in situ hybridization (FISH) 
      with whole chromosome painting probes used to identify chromosomes in cells 
      growing on glass chamber slides (2 probes/slide). A variety of sizes and shapes 
      of NBs were observed. Some NBs had a large connection with the main nucleus 
      (>(1/4) of the NB diameter), others hada smaller connection (<(1/4) of the NB 
      diameter), some were circular and positioned close to the nucleus, while some 
      resided in the cytoplasm separated from the nucleus or connected by a thin 
      chromatin strand. We had hypothesized that NBs would progress in the process of 
      budding until separation occurred, but this was not proven by time-lapse 
      photography studies performed for 20 hours. From 1,126 cells scored in the 
      unexposed cultures, 10.39 % of cells carried NBs, while from 1,108 cells scored 
      in the AZT-exposed cultures 29.16% of cells carried NBs (p = 0.001). In 
      AZT-exposed cells there were a total of 322 NBs scored; 46.6% or 150 NBs 
      contained positive signals for one or both probes used, while 53% or 172 NBs had 
      no probe signal. In addition, FISH analysis showed no preferential localization 
      of any chromosome within the NBs. Among the NBs that carried no probe signal, the 
      presence of positive signals with inversion of DAPI imaging demonstrated 
      centromeric content. It has been hypothesized that NBs occur as a result of 
      expulsion of amplified DNA from the main nucleus; however, this data demonstrates 
      that NBs may contain any chromosome, suggesting that NBs do not consist of just 
      amplified DNA.
CI  - Copyright 2010 S. Karger AG, Basel.
FAU - Dutra, A
AU  - Dutra A
AD  - Cytogenetics and Microscopy Core, National Human Genome Research Institute, 
      National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA.
FAU - Pak, E
AU  - Pak E
FAU - Wincovitch, S
AU  - Wincovitch S
FAU - John, K
AU  - John K
FAU - Poirier, M C
AU  - Poirier MC
FAU - Olivero, O A
AU  - Olivero OA
LA  - eng
PT  - Journal Article
DEP - 20100420
PL  - Switzerland
TA  - Cytogenet Genome Res
JT  - Cytogenetic and genome research
JID - 101142708
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Xeroderma Pigmentosum Group A Protein)
RN  - 0 (Xpa protein, mouse)
RN  - 4B9XT59T7S (Zidovudine)
SB  - IM
MH  - Animals
MH  - Anti-HIV Agents/*toxicity
MH  - Cell Nucleus/*drug effects
MH  - Mice
MH  - Tumor Suppressor Protein p53/genetics
MH  - Xeroderma Pigmentosum Group A Protein/genetics
MH  - Zidovudine/*toxicity
PMC - PMC2883836
EDAT- 2010/04/22 06:00
MHDA- 2010/06/15 06:00
PMCR- 2011/05/01
CRDT- 2010/04/22 06:00
PHST- 2010/04/22 06:00 [entrez]
PHST- 2010/04/22 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - 000298794 [pii]
AID - cgr0128-0105 [pii]
AID - 10.1159/000298794 [doi]
PST - ppublish
SO  - Cytogenet Genome Res. 2010;128(1-3):105-10. doi: 10.1159/000298794. Epub 2010 Apr 
      20.