PMID- 24582839
OWN - NLM
STAT- MEDLINE
DCOM- 20140628
LR  - 20150311
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 762
DP  - 2014 Apr
TI  - Chromosome loss caused by DNA fragmentation induced in main nuclei and 
      micronuclei of human lymphoblastoid cells treated with colcemid.
PG  - 10-6
LID - S0027-5107(14)00025-6 [pii]
LID - 10.1016/j.mrfmmm.2014.02.002 [doi]
AB  - Aneuploidy, a change in the number of chromosomes, plays an essential role in 
      tumorigenesis. Our previous study demonstrated that a loss of a whole chromosome 
      is induced in human lymphocytes by colcemid, a well-known aneugen. Here, to 
      clarify the mechanism for colcemid-induced chromosome loss, we investigated the 
      relationship between chromosome loss and DNA fragmentation in human 
      lymphoblastoid cells treated with colcemid (an aneugen) compared with methyl 
      methanesulfonate (MMS; a clastogen). We analyzed the number of fluorescence in 
      situ hybridization (FISH) signals targeted for a whole chromosome 2 in 
      cytokinesis-blocked binucleated TK6 cells and WTK-1 cells treated with colcemid 
      and MMS, and concurrently detected DNA fragmentation by terminal deoxynucleotidyl 
      transferase dUTP nick end labeling (TUNEL) assay. Results revealed that DNA 
      fragmentation occurred in 60% of all binucleated TK6 cells harboring 
      colcemid-induced chromosome loss (30% of micronuclei and 30% of main nuclei). DNA 
      fragmentation was observed in colcemid-induced micronuclei containing a whole 
      chromosome but not in MMS-induced micronuclei containing chromosome fragments. In 
      contrast, colcemid-induced nondisjunction had no effect on induction of DNA 
      fragmentation, suggesting that DNA fragmentation was triggered by micronuclei 
      containing a whole chromosome but not by micronuclei containing chromosome 
      fragments or nondisjunction. In addition, the frequency of binucleated cells 
      harboring chromosome loss with DNA fragmentation in micronuclei or main nuclei 
      was higher in wild-type p53 TK6 cells than in mutated-p53 WTK-1 cells treated 
      with colcemid. Taken together, these present and previous results suggest that 
      colcemid-induced chromosome loss is caused by DNA fragmentation, which is 
      triggered by a micronucleus with a whole chromosome and controlled by the 
      p53-dependent pathway.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Yamamoto, Mika
AU  - Yamamoto M
AD  - Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, 
      Yodogawa-ku, Osaka 532-8514, Japan; Laboratory of Radiation Biology, Department 
      of Biological Science, Graduate School of Science, Osaka Prefecture University, 
      1-2, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
FAU - Wakata, Akihiro
AU  - Wakata A
AD  - Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, 
      Yodogawa-ku, Osaka 532-8514, Japan.
FAU - Aoki, Yoshinobu
AU  - Aoki Y
AD  - Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, 
      Yodogawa-ku, Osaka 532-8514, Japan.
FAU - Miyamae, Yoichi
AU  - Miyamae Y
AD  - Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, 
      Yodogawa-ku, Osaka 532-8514, Japan.
FAU - Kodama, Seiji
AU  - Kodama S
AD  - Laboratory of Radiation Biology, Department of Biological Science, Graduate 
      School of Science, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Sakai, 
      Osaka 599-8570, Japan. Electronic address: kodama@riast.osakafu-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20140227
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Mutagens)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - AT5C31J09G (Methyl Methanesulfonate)
RN  - Z01IVE25KI (Demecolcine)
SB  - IM
MH  - Aneuploidy
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 2
MH  - DNA Fragmentation/*drug effects
MH  - Demecolcine/*pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - In Situ Nick-End Labeling
MH  - Lymphocytes/drug effects/metabolism/pathology
MH  - Methyl Methanesulfonate/pharmacology
MH  - Micronuclei, Chromosome-Defective/*drug effects
MH  - Mutagens/*pharmacology
MH  - Nondisjunction, Genetic
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/genetics/metabolism
OTO - NOTNLM
OT  - Aneuploidy
OT  - Chromosome loss
OT  - DNA fragmentation
OT  - FISH
OT  - Micronucleus
OT  - TUNEL assay
EDAT- 2014/03/04 06:00
MHDA- 2014/06/29 06:00
CRDT- 2014/03/04 06:00
PHST- 2013/09/02 00:00 [received]
PHST- 2013/12/19 00:00 [revised]
PHST- 2014/02/18 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/06/29 06:00 [medline]
AID - S0027-5107(14)00025-6 [pii]
AID - 10.1016/j.mrfmmm.2014.02.002 [doi]
PST - ppublish
SO  - Mutat Res. 2014 Apr;762:10-6. doi: 10.1016/j.mrfmmm.2014.02.002. Epub 2014 Feb 
      27.