PMID- 12714688
OWN - NLM
STAT- MEDLINE
DCOM- 20040123
LR  - 20190513
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 18
IP  - 3
DP  - 2003 May
TI  - Noscapine hydrochloride-induced numerical aberrations in cultured human 
      lymphocytes: a comparison of FISH detection methods and multiple end-points.
PG  - 235-42
AB  - The cytokinesis block in vitro micronucleus (MN) assay in combination with CREST 
      staining and fluorescence in situ hybridization (FISH) with chromosome-specific 
      DNA probes allows mechanistic information on the induction of numerical 
      chromosomal aberrations to be obtained through a rapid and simple microscopic 
      analysis. These techniques can now be used to investigate relationships between 
      the induction of chromosomal loss, non-disjunction and polyploidy by 
      aneuploidy-inducing agents. In the present study, we treated 72 h cultured 
      lymphocytes for the last 24 h of culture with various concentrations of the cough 
      medicine noscapine hydrochloride (NOS) (3.9-120 micro g/ml) in the presence of 
      either cytochalasin B (CYB) (3 micro g/ml) or 5-bromo-2'-deoxyuridine (BrdU) (1 
      micro M). Using the CREST staining modified MN assay in the CYB-treated cultures, 
      we detected significant increases in CREST-positive but not CREST-negative MN in 
      both binucleated and, to a lesser extent, mononucleated cells, demonstrating the 
      ability of this compound to induce chromosomal loss. In addition, using FISH with 
      chromosome 1- and 9-specific classical satellite probes, a significant induction 
      of chromosomal non-disjunction in the binucleated lymphocytes and polyploidy in 
      the mononucleated lymphocytes was seen, indicating that polyploidy induced by NOS 
      may occur without progression through a normal anaphase and/or telophase. In the 
      BrdU-treated cultures, a dose-dependent induction of hypodiploidy, hyperdiploidy 
      and polyploidy was observed using FISH with a chromosome 9-specific 
      alpha-satellite probe in the labeled cells. By comparison, in the unlabeled 
      non-cycling cells, only a slight increase in hyperdiploidy/polyploidy but not 
      hypodiploidy was seen. A comparison of the effects seen at different 
      concentrations shows that at the lower effective concentrations, all three types 
      of numerical aberrations, chromosomal loss, non-disjunction and polyploidy, 
      contributed to the numerical aberrations seen, whereas at the highest 
      concentration tested, polyploidy was the predominant alteration. These studies 
      indicate that FISH in combination with CYB or BrdU immunfluorescent staining can 
      be sensitive tools for the identification of aneuploidy-inducing agents.
FAU - Schuler, M
AU  - Schuler M
AD  - Environmental Toxicology Graduate Program, University of California, Riverside, 
      CA 92521, USA.
FAU - Muehlbauer, P
AU  - Muehlbauer P
FAU - Guzzie, P
AU  - Guzzie P
FAU - Eastmond, D A
AU  - Eastmond DA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Aneugens)
RN  - 0 (Antitussive Agents)
RN  - 0 (Biomarkers)
RN  - 8V32U4AOQU (Noscapine)
SB  - IM
MH  - Aneugens/*pharmacology
MH  - *Aneuploidy
MH  - Antitussive Agents/*pharmacology
MH  - Biomarkers
MH  - Cell Division/drug effects
MH  - Chromosomes, Human
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/*drug effects
MH  - Noscapine/*pharmacology
EDAT- 2003/04/26 05:00
MHDA- 2004/01/24 05:00
CRDT- 2003/04/26 05:00
PHST- 2003/04/26 05:00 [pubmed]
PHST- 2004/01/24 05:00 [medline]
PHST- 2003/04/26 05:00 [entrez]
AID - 10.1093/mutage/18.3.235 [doi]
PST - ppublish
SO  - Mutagenesis. 2003 May;18(3):235-42. doi: 10.1093/mutage/18.3.235.