Genotoxicity of dihydroabikoviromycin, a secondary metabolite of Streptomyces anulatus.
The potential genotoxicity of dihydroabikoviromycin was assessed in bacterial and sister-chromatid exchange (SCE) test systems. Direct cytotoxicity was also assayed using bioluminescence methods to screen for differences in cell viability among different tumour cell lines following exposure to the drug. Differential killing tests with Escherichia coli WP2 and its repair-deficient derivative CM871 indicated that a functional DNA repair system was protective against the action of dihydroabikoviromycin, implying that this compound causes some form of DNA damage and is almost certainly therefore genotoxic. Dose-dependent reversion from His- to His+ with dihydroabikoviromycin was observed in the Ames test with Salmonella typhimurium TA100, but not in frameshift tester strain TA98. Dihydroabikoviromycin also induced the sfiA gene, as indicated by beta-galactosidase induction in an SOS-chromotest with E. coli PQ37 strain. A dose-related increase in SCEs by dihydroabikoviromycin was observed in CHO cells. Growth of tumour cells was also suppressed by dihydroabikoviromycin at a dose of 10 micrograms/ml.
Holmalahti
J
J
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Mäki-Paakkanen
J
J
Kangas
L
L
von Wright
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D009153:Mutagens / Q000633:toxicity*; D010880:Piperidines / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D009153:Mutagens; D010880:Piperidines; C007394:dihydroabikoviromycin; D004247:DNA