Mitochondrial and nuclear mutagenicity of ellipticine and derivatives in the yeast Saccharomyces cerevisiae.
Haploid strains of the yeast Saccharomyces cerevisiae were tested for their sensitivity to ellipticine and nine derivatives; some of them exhibiting antitumor properties. Different mutagenic properties of ellipticines are described. Charged ellipticines, which were ineffective in Ames' bacterial assay, were found to be potent inducers of the mitochondrial p- mutation: induction proceeded even in the absence of growth. Uncharged ellipticines increased mitochondrial antibiotic resistance mutations, whereas charged derivatives decreased them. Ellipticine derivatives enhanced, reduced, or did not change the reversion frequencies of nuclear auxotrophic markers. The result depended on the strain being tested: no structure-effect relationship existed. As some ellipticine derivatives were mutagenic in Saccharomyces cerevisiae despite being ineffective in Ames' assay, multiple tests should be used to check that chemotherapeutic drugs are devoid of mutagenic properties.
D000470:Alkaloids / Q000633:toxicity*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects*; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004611:Ellipticines / Q000633:toxicity*; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D010101:Oxygen Consumption / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D003470:Culture Media; D004611:Ellipticines; D009153:Mutagens; D005947:Glucose