Hyperhaploid and tetraploid sperm detected in men who ingested ultra-high doses of diazepam

Journal Article · Wed Oct 01 04:00:00 EDT 1997 · Environmental and Molecular Mutagenesis

OSTI ID:530828

Baumgartner, A ^[1]; Adler, I D; Schmid, T E ^[2]

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1. Lawrence Livermore National Lab., CA (United States)
2. GSF-Inst. Saeugetiergenetik, Neuherberg (Germany); and others

Diazepam is widely administered as a sedative, muscle relaxant and anxiolytic drug. Five young non-smoking men who were hospitalized after their suicide attempt using diazepam, {approximately}1-7 mg/kg (oral intake), provided semen samples 40-50 days and {approximately}100 days after exposure to assess drug effects on meiotic cells and to evaluate persistence. Five healthy men served as local clinical controls. A multicolor FISH assay was applied to detect aneuploidy for chromosome X, Y, and 21 in sperm. Sex ratios were not significantly different from 1:1 among 133,143 cells analyzed. The 40-day samples showed an increase in several sperm aneuploidy groups: disomy 21 (1.5 fold, p=0.04); disomy X (2.7 fold, p=0.0006), and XY aneuploidy (1.6 folk, p=0 0.017). The results for {approximately}100 days after exposure were similar to controls suggesting that hyperhaploidy effects may not persist. Phase contrast microscopy was used to identify flagellated tetraploid sperm, i.e., X-X-Y-Y-21-21-21-21. Tetraploid sperm were found among 8 semen samples provided by five patients (1.4 {+-} 1.2 per 10,000 cells; >80,000 cells) while none were detected among >50,000 cells from healthy men. Our findings are consistent with the possible aneuploidy-inducing effect of diazepam during male meiosis but further studies are needed before these results can be extrapolated to therapeutic dosing because suicide patients are a highly exposed cohort and other confounding factors (alcohol, drugs, antidotes) cannot be ruled out.

• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 530828
• Report Number(s): CONF-9704100--; CNN: Contract EV5V-CT94-0403
• Journal Information: Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.28 Vol. 29; ISSN 0893-6692; ISSN EMMUEG
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANEUPLOIDY
DIAZO COMPOUNDS
DRUGS
GENETIC EFFECTS
MEN
SPERMATOZOA
STRESS RELAXATION