PMID- 23726961
OWN - NLM
STAT- MEDLINE
DCOM- 20130905
LR  - 20151119
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 755
IP  - 1
DP  - 2013 Jul 4
TI  - New DNA probes to detect aneugenicity in rat bone marrow micronucleated cells by 
      a pan-centromeric FISH analysis.
PG  - 73-80
LID - S1383-5718(13)00144-7 [pii]
LID - 10.1016/j.mrgentox.2013.05.011 [doi]
AB  - When characterizing the genotoxicity of chemicals that induce micronuclei, it is 
      practical to be able to classify the chemicals as aneugens or clastogens. This 
      classification gives information on the mechanistic properties of chemicals and 
      is indispensable for setting the threshold safety margins for genotoxicity in 
      pharmaceutical development. A widely used method for detecting aneugens is 
      fluorescence in situ hybridization (FISH) but, even though the rat is an 
      experimental animal generally used in preclinical studies in drug development, 
      DNA probes that hybridize to all the centromeres of rat chromosomes have not yet 
      been established. In the present study, in addition to the previously known 
      satellite I sequence, we identified two novel satellite sequences, satellite II 
      and satellite III, from the rat genome database. DNA probes with a mixture of 
      these satellite DNA sequences were used to establish a FISH method for 
      pan-centromeric staining of rat chromosomes. To confirm the feasibility of the 
      method, vinblastine (VBS) and mitomycin C (MMC) were administered to rats as a 
      typical aneugen and clastogen, respectively. Micronucleated polychromatic 
      erythrocytes (MNPCE) from bone marrow were enriched by sorting in flow cytometry 
      and subjected to the FISH method. As a result, the ratio of centromere-positive 
      MNPCE increased in VBS-treated rats but not in MMC-treated ones. Since the FISH 
      method using the novel DNA probes clearly discriminates the aneugens from the 
      clastogens, we suggest this method as a useful tool for providing mechanistic 
      information for micronucleus induction in vivo.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Takeiri, Akira
AU  - Takeiri A
AD  - Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. takeiriakr@chugai-pharm.co.jp
FAU - Motoyama, Shigeki
AU  - Motoyama S
FAU - Matsuzaki, Kaori
AU  - Matsuzaki K
FAU - Harada, Asako
AU  - Harada A
FAU - Taketo, Junko
AU  - Taketo J
FAU - Katoh, Chiaki
AU  - Katoh C
FAU - Tanaka, Kenji
AU  - Tanaka K
FAU - Mishima, Masayuki
AU  - Mishima M
LA  - eng
PT  - Journal Article
DEP - 20130529
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Aneugens)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (DNA Probes)
RN  - 0 (DNA, Satellite)
RN  - 0 (Mutagens)
RN  - 0 (Tubulin Modulators)
RN  - 50SG953SK6 (Mitomycin)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - SML2Y3J35T (Colchicine)
SB  - IM
MH  - Aneugens/*toxicity
MH  - Animals
MH  - Antibiotics, Antineoplastic/toxicity
MH  - Base Sequence
MH  - Bone Marrow/*drug effects
MH  - Centromere/*drug effects/genetics
MH  - Chromosomes/genetics
MH  - Colchicine/toxicity
MH  - *DNA Probes
MH  - DNA, Satellite/analysis/genetics
MH  - Erythrocytes/drug effects
MH  - Flow Cytometry
MH  - *In Situ Hybridization, Fluorescence
MH  - Male
MH  - Micronuclei, Chromosome-Defective/*drug effects
MH  - Micronucleus Tests
MH  - Mitomycin/toxicity
MH  - Molecular Sequence Data
MH  - Mutagens/*toxicity
MH  - Rats
MH  - Sequence Homology, Nucleic Acid
MH  - Tubulin Modulators/toxicity
MH  - Vinblastine/toxicity
OTO - NOTNLM
OT  - Aneugen
OT  - Centromere
OT  - FISH
OT  - Rat
OT  - Satellite DNA
EDAT- 2013/06/04 06:00
MHDA- 2013/09/06 06:00
CRDT- 2013/06/04 06:00
PHST- 2013/03/06 00:00 [received]
PHST- 2013/04/27 00:00 [revised]
PHST- 2013/05/14 00:00 [accepted]
PHST- 2013/06/04 06:00 [entrez]
PHST- 2013/06/04 06:00 [pubmed]
PHST- 2013/09/06 06:00 [medline]
AID - S1383-5718(13)00144-7 [pii]
AID - 10.1016/j.mrgentox.2013.05.011 [doi]
PST - ppublish
SO  - Mutat Res. 2013 Jul 4;755(1):73-80. doi: 10.1016/j.mrgentox.2013.05.011. Epub 
      2013 May 29.