Modes of genotoxicity of a macromolecular antibiotic, SN-07, a novel type of interstrand DNA cross-linker.
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.
Yajima
N
N
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Ishida
S
S
Miyata
N
N
Kishi
T
T
Kawanishi
G
G
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004249:DNA Damage; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; C047795:SN-07