PMID- 9585265
OWN - NLM
STAT- MEDLINE
DCOM- 19980520
LR  - 20191024
IS  - 0893-6692 (Print)
IS  - 0893-6692 (Linking)
VI  - 31
IP  - 3
DP  - 1998
TI  - Dose-response studies of the induction of hyperdiploidy and polyploidy by 
      diethylstilbestrol and 17beta-estradiol in cultured human lymphocytes using 
      multicolor fluorescence in situ hybridization.
PG  - 263-73
AB  - Diethylstilbestrol (DES) and 17beta-estradiol (E2) are known inducers of 
      aneuploidy and polyploidy in vivo and in vitro. Isolated human lymphocytes were 
      treated with the stilbene estrogen DES (0.05-50 microM) and the steroid estrogen 
      E2 (0.05-75 microM) in culture. Multicolor fluorescence in situ hybridization 
      (FISH) with DNA probes for the centromere and adjacent heterochromatin regions of 
      chromosomes 1, 9, and 16 was used to detect hyperdiploidy, polyploidy, and 
      chromosomal breakage affecting these chromosomes. Using this FISH technique, 
      significant nonlinear increases in hyperdiploidy were observed with both 
      compounds, whereas no induction of chromosomal breakage affecting the pericentric 
      heterochromatin regions of chromosomes 1, 9, and 16 could be detected. DES 
      induced a maximum of approximately 13% hyperdiploid cells at 30 microM, whereas 
      E2 showed its highest induction at 75 microM with 7% hyperdiploid cells. To 
      distinguish hyperdiploidy from polyploidy, a FISH labeling strategy to detect 
      multiple chromosomes simultaneously was established. Using this approach, we 
      could show that most of the cells showing multiple hybridization regions after 
      treatment with both chemicals were most likely the result of polyploidy rather 
      than true hyperdiploidy. These results indicate that the induction of 
      hyperdiploidy/polyploidy with DES and E2 show sublinear dose-response 
      relationships with likely threshold concentrations in human lymphocytes and that 
      FISH with multiple probes targeting different chromosomes can be used to estimate 
      hyperdiploidy and polyploidy frequencies.
FAU - Schuler, M
AU  - Schuler M
AD  - Department of Entomology, University of California, Riverside 92521, USA.
FAU - Hasegawa, L
AU  - Hasegawa L
FAU - Parks, R
AU  - Parks R
FAU - Metzler, M
AU  - Metzler M
FAU - Eastmond, D A
AU  - Eastmond DA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoxazoles)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Fluoro-Green)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Quinolinium Compounds)
RN  - 1325-87-7 (Cascade Blue)
RN  - 143413-85-8 
      (1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium)
RN  - 4TI98Z838E (Estradiol)
RN  - 731DCA35BT (Diethylstilbestrol)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Benzimidazoles
MH  - Benzoxazoles
MH  - Cells, Cultured
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human/*drug effects/ultrastructure
MH  - Diethylstilbestrol/administration & dosage/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Estradiol/administration & dosage/*pharmacology
MH  - Fluorescein-5-isothiocyanate
MH  - Fluorescent Dyes
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lymphocytes/*drug effects/ultrastructure
MH  - Organometallic Compounds
MH  - Organophosphorus Compounds
MH  - *Polyploidy
MH  - Quinolinium Compounds
EDAT- 1998/05/19 02:03
MHDA- 2000/06/20 09:00
CRDT- 1998/05/19 02:03
PHST- 1998/05/19 02:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/05/19 02:03 [entrez]
AID - 10.1002/(SICI)1098-2280(1998)31:3<263::AID-EM8>3.0.CO;2-L [pii]
AID - 10.1002/(sici)1098-2280(1998)31:3<263::aid-em8>3.0.co;2-l [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 1998;31(3):263-73. doi: 
      10.1002/(sici)1098-2280(1998)31:3<263::aid-em8>3.0.co;2-l.