Cytotoxicity and genotoxicity of xenoclauxin and desacetyl duclauxin from Penicillium duclauxii (Delacroix)

• Published in: Cell biology and toxicology Vol. 1; no. 2; p. 1
• Main Authors: Kawai, K, Shiojiri, H, Nakamaru, T, Nozawa, Y, Sugie, S, Mori, H, Kato, T, Ogihara, Y
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.1985
• Subjects: Animals; Antineoplastic Agents; Chemical Phenomena; Chemistry; Chromones - adverse effects; DNA Repair - drug effects; Leukemia L1210 - drug therapy; Mitochondria, Liver - drug effects; Mutagens; Oxidation-Reduction - drug effects; Oxygen Consumption - drug effects; Penicillium - metabolism; Phosphorylation
• ISSN: 0742-2091
• DOI: 10.1007/BF00717786

The duclauxin derivatives xenoclauxin and desacetylduclauxin were examined for their effects on the growth of L-1210 murine leukemia cells, on the induction of DNA repair in the rat and mouse hepatocyte primary culture (HPC/DNA repair test), and on oxidative phosphorylation in mitochondria from rat livers in comparison to duclauxin. Both derivatives inhibited the growth of L-1210 culture cells as strongly as duclauxin. Duclauxin derivatives were negative in the HPC/DNA repair test. Xenoclauxin exhibited a potent uncoupling effect accompanying a marked depression of state 3 respiration of mitochondria in a similar fashion to that of duclauxin. Desacetylduclauxin significantly inhibited the state 3 respiration without causing uncoupling of oxidative phosphorylation in mitochondria. These results strongly suggest that xenoclauxin and desacetylduclauxin from Penicillium duclauxii are not genotoxic but are cytotoxic mainly due to their potent inhibition of ATP synthesis in mitochondria.