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Modes of genotoxicity of a macromolecular antibiotic, SN-07, a novel type of interstrand DNA cross-linker.

Abstract
The modes of genotoxicity of a novel macromolecular antitumor antibiotic (SN-07) were examined using both prokaryotic and eukaryotic cells in vitro. The antibiotic induced a frameshift-type reverse mutation in Ames Salmonella typhimurium TA98 at 1.6-400 ng/plate with and without S9 mix. SN-07 also induced chromosomal aberrations and a forward mutation (6-TGr) in Chinese hamster V79 cells after 1 h treatment at 12.5-100 ng/ml without metabolic activation. The alkaline elution technique revealed that SN-07 induced interstrand DNA cross-linking dose-dependently after treatment with 2.5-10 micrograms/ml for 1 h followed by elution at pH 12.1, but it did not induce the dose-dependent cross-linking after the same treatment followed by elution at pH 12.6. It was also found that SN-07 induced single-strand DNA breaks (pH 12.1) and alkali-labile (pH 12.6) sites after treatment with 0.1-10 micrograms/ml for 1 h followed by 24-h post-incubation.
AuthorsN Yajima, S Ishida, N Miyata, T Kishi, G Kawanishi
JournalMutation research (Mutat Res) Vol. 210 Issue 1 Pg. 165-72 (Jan 1989) ISSN: 0027-5107 [Print] Netherlands
PMID2462669 (Publication Type: Journal Article)
Chemical References
  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Cross-Linking Reagents
  • SN-07
Topics
  • Animals
  • Anthracyclines
  • Antibiotics, Antineoplastic (toxicity)
  • Cells, Cultured
  • Chromosome Aberrations
  • Cricetinae
  • Cross-Linking Reagents
  • DNA Damage
  • Mutagenicity Tests
  • Salmonella typhimurium (drug effects)

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