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Absence of liver DNA fragmentation in rats treated with high oral doses of 32 benzodiazepine drugs.

Authors
  • Carlo, P
  • Finollo, R
  • Ledda, A
  • Brambilla, G
Type
Published Article
Journal
Fundamental and applied toxicology : official journal of the Society of Toxicology
Publication Date
Jan 01, 1989
Volume
12
Issue
1
Pages
34–41
Identifiers
PMID: 2925017
Source
Medline
License
Unknown

Abstract

Literature data on mutagenic-carcinogenic activity of benzodiazepines are scarce, restricted to few of them, and contradictory. Consequently, in order to provide additional information for the assessment of the genotoxic risk connected with the use of this family of drugs, 32 benzodiazepines of various chemical structure have been tested for their capability to induce DNA damage in vivo, which is considered a sensitive index of potential mutagenic-carcinogenic activity. The frequency of DNA single-strand breaks and/or alkali-labile sites was checked in the liver of rats given orally a single dose (1 mmol/kg) or 15 successive daily doses (0.2 mmol/kg) by the use of a new viscometric technique capable of detecting one DNA lesion per 10(10) Da. Statistically significant changes of viscometric parameters indicative of liver DNA fragmentation were absent with all 32 benzodiazepines, after both acute and subacute treatments. Since the doses tested in rats were from 100 to more than 5000 times higher than doses usually administered to humans, these negative results are in favor of the absence of mutagenic-carcinogenic effects in patients taking benzodiazepines.

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