PMID- 10635342
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 446
IP  - 2
DP  - 1999 Dec 13
TI  - Persistence of chromosomal alterations affecting the 1cen-q12 region in a human 
      lymphoblastoid cell line exposed to diepoxybutane and mitomycin C.
PG  - 193-203
AB  - Multicolor fluorescence in situ hybridization (FISH) with tandem-labeling probes 
      for the 1cen-q12 region is a potential biomarker for the detection of structural 
      chromosomal aberrations (CAs) in human cells. To determine the suitability of 
      this technique for biomonitoring humans exposed to 1,3-butadiene (BD) and to 
      characterize the alterations induced as well as their stability over time, the 
      human lymphoblastoid cell line AZH-1 was treated with 5 microM diepoxybutane 
      (DEB) or the positive control mitomycin C (MMC; 0.1 microM) for 24 h. Following 
      the removal of the test chemicals, cell cultures were grown for an additional 19 
      days in the absence of the test compound. Using the tandem FISH technique, 
      aliquots from the main cultures were examined for the induction of CAs affecting 
      the 1cen-q12 region at various intervals. A significant increase in chromosomal 
      breakage/exchanges affecting the 1cen-q12 region was seen in both the DEB- and 
      MMC-treated interphase and metaphase cells. The damage peaked at approximately 48 
      h following the addition of the test compound and declined with time. However, at 
      day 20, the frequency of aberrant cells was still significantly higher than the 
      control levels. For comparison, the frequency of micronuclei (MN) formed and 
      their origin was determined using the cytochalasin B-modified MN assay and FISH 
      with a pancentromeric probe. Showing a similar pattern, the frequency of 
      centronere-negative MN peaked at 48 h, but however was not significantly elevated 
      above control levels at 20 days. At early time points, aberrations detected using 
      the FISH assay consisted of nearly equal proportions of unstable- and stable-type 
      aberrations, while at the later time points, translocations were the predominant 
      aberration type. In addition, the use of tandem-label FISH in combination with 
      BrdU-immunfluorescence staining, showed that almost identical frequencies of 
      structural aberrations could be seen in actively replicating and non-replicating 
      cell populations. These studies indicate that a small but significant proportion 
      of the alterations detected using this FISH technique persists over time and that 
      this technique may be valuable for biomonitoring chromosomal alterations in 
      BD-exposed populations.
FAU - Murg, M N
AU  - Murg MN
AD  - Environmental Toxicology Graduate Program, University of California, Riverside 
      92521, USA.
FAU - Schuler, M
AU  - Schuler M
FAU - Eastmond, D A
AU  - Eastmond DA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 50SG953SK6 (Mitomycin)
RN  - 60OB65YNAB (diepoxybutane)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Bromodeoxyuridine/analysis/metabolism
MH  - Cell Cycle/drug effects/genetics
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 1/*drug effects
MH  - Environmental Monitoring/methods
MH  - Epoxy Compounds/*toxicity
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Lymphocyte Activation
MH  - Lymphocytes/cytology/*drug effects/physiology
MH  - Micronucleus Tests
MH  - Mitomycin/*toxicity
MH  - Mutagens/*toxicity
MH  - Staining and Labeling/methods
MH  - Time Factors
EDAT- 2000/01/15 00:00
MHDA- 2000/01/15 00:01
CRDT- 2000/01/15 00:00
PHST- 2000/01/15 00:00 [pubmed]
PHST- 2000/01/15 00:01 [medline]
PHST- 2000/01/15 00:00 [entrez]
AID - S1383-5718(99)00184-9 [pii]
AID - 10.1016/s1383-5718(99)00184-9 [doi]
PST - ppublish
SO  - Mutat Res. 1999 Dec 13;446(2):193-203. doi: 10.1016/s1383-5718(99)00184-9.