PMID- 11152967
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20191210
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 490
IP  - 1
DP  - 2001 Jan 25
TI  - Detection of aneuploidy in rodent and human sperm by multicolor FISH after 
      chronic exposure to diazepam.
PG  - 11-9
AB  - Aneuploidy induction in male germ cells of mice and men after chronic exposure to 
      diazepam (DZ; CAS 439-14-5; Valium was assessed by multicolor fluorescence in 
      situ hybridization (FISH). DZ, a widely administered sedative and muscle 
      relaxant, was proposed to act as an aneugen by disturbing spindle function in 
      various assay systems. Male mice were treated by oral intubation with 3mg/kg DZ 
      once or daily for 14 consecutive days. At 22 days after the last treatment, 
      epididymal sperm were collected from the caudae epididymes. Evaluation of 
      aneuploid and diploid sperm (10,000 sperm per animal) was performed by multicolor 
      FISH employing DNA probes specific for chromosomes X, Y, and 8 simultaneously. We 
      found a significant increase in the frequency of disomy 8 in subchronically 
      DZ-treated mice when compared to the concurrent solvent control group (2.4-fold; 
      P<0.01), while no increase was detected for sex-chromosome hyperhaploidies. No 
      effect was seen when mice were treated with a single dose (3mg/kg DZ). In a 
      parallel human approach, two men were evaluated who chronically ingested 
      >0.3mg/kg/d DZ for more than 6 months. Multicolor FISH was applied to human sperm 
      probing for chromosomes X, Y, and 13. Frequencies for sperm with disomy 13, 
      disomy X, and total sex-chromosomal disomies were found to be elevated among the 
      two subjects after chronic DZ-exposure compared to control subjects. In 
      conclusion, the results indicate that diazepam acts as an aneugen during meiosis 
      in male spermatogenesis, both in mice and humans. The quantitative comparison 
      indicates that humans may be at least 10 times more sensitive than mice for 
      aneuploidy induction by DZ during male meiosis.
FAU - Baumgartner, A
AU  - Baumgartner A
AD  - Institute of Experimental Genetics, GSF-National Research Center for Environment 
      and Health, D-85758, Neuherberg, Germany.
FAU - Schmid, T E
AU  - Schmid TE
FAU - Schuetz, C G
AU  - Schuetz CG
FAU - Adler, I D
AU  - Adler ID
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (DNA Probes)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Adult
MH  - *Aneuploidy
MH  - Animals
MH  - Chromosomes, Human, Pair 13
MH  - DNA Probes
MH  - Diazepam/*adverse effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Spermatozoa/*drug effects/physiology
MH  - X Chromosome
MH  - Y Chromosome
EDAT- 2001/01/12 11:00
MHDA- 2001/04/03 10:01
CRDT- 2001/01/12 11:00
PHST- 2001/01/12 11:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2001/01/12 11:00 [entrez]
AID - S1383571800001418 [pii]
AID - 10.1016/s1383-5718(00)00141-8 [doi]
PST - ppublish
SO  - Mutat Res. 2001 Jan 25;490(1):11-9. doi: 10.1016/s1383-5718(00)00141-8.