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Genotoxicity of vanadium compounds in yeast and cultured mammalian cells
Abstract:
The ability of vanadium compounds to induce genetic activity was investigated in D7 and D61M strains of Saccharomyces cerevisiae and in Chinese hamster V79 cell line. In our previous work, ammonium metavanadate (pentavalent form, V5) induced mitotic gene conversion and point reverse mutation in the D7 strain of yeast. The genotoxicity was reduced by the presence of S9 fraction, which probably reduced pentavalent vanadium to the tetravalent form. In the present study, vanadyl sulfate (tetravalent form, V4) induced no convertants and revertants in yeast cells harvested from stationary growth phase. With yeast cells from logarithmic growth phase, which contain high levels of cytochrome P-450, a significant increase in genetic effects was observed. Further experiments, performed by treating cells harvested from logarithmic growth phase in the presence of cytochrome P-450 inhibitors, indicated that the monooxygenase system influenced the genotoxicity of metavanadate while the genetic activity of vanadyl remained unaffected. Aneuploidy effect in the D61M strain of Saccharomyces cerevisiae was induced by either V5 or V4, confirming that vanadium compounds are potentially antitubulin agents in eukaryotic cells. Although these compounds are very toxic in V79 cells, no mutagenic effect was observed in the presence or in the absence of S9 fraction.
Insights
Vanadium compounds show genotoxicity in yeast, with tetravalent vanadium (V4) requiring specific cell conditions. Both V4 and pentavalent vanadium (V5) induce aneuploidy, suggesting antitubulin activity in eukaryotic cells.
Area of Science:
- Biochemistry
- Genetics
- Toxicology
Background:
- Vanadium compounds, including pentavalent vanadium (V5) and tetravalent vanadium (V4), are known to possess genotoxic potential.
- Previous studies indicated V5 induces gene conversion and mutation in yeast, with reduced genotoxicity in the presence of S9 fraction.
- The role of cellular factors like cytochrome P-450 in vanadium genotoxicity requires further elucidation.
Purpose of the Study:
- To investigate the genotoxic effects of different vanadium oxidation states (V4 and V5) in yeast strains (Saccharomyces cerevisiae D7, D61M) and Chinese hamster V79 cells.
- To determine the influence of cell growth phase and cytochrome P-450 on vanadium-induced genotoxicity.
- To assess the potential of vanadium compounds as antitubulin agents.
Main Methods:
- Yeast strains D7 and D61M were treated with ammonium metavanadate (V5) and vanadyl sulfate (V4).
- Experiments were conducted using yeast cells from stationary and logarithmic growth phases, with and without S9 fraction and cytochrome P-450 inhibitors.
- Chinese hamster V79 cells were treated to assess mutagenicity and toxicity.
Main Results:
- Vanadyl sulfate (V4) showed genotoxicity in yeast cells from logarithmic growth phase, which have higher cytochrome P-450 levels, but not in stationary phase cells.
- The monooxygenase system influenced V5 genotoxicity, while V4 genotoxicity remained unaffected by cytochrome P-450 inhibitors.
- Both V4 and V5 induced aneuploidy in yeast, suggesting antitubulin activity. V79 cells exhibited high toxicity but no mutagenicity.
Conclusions:
- Vanadium compounds exhibit differential genotoxicity dependent on oxidation state and cellular metabolic conditions.
- The monooxygenase system plays a role in the genotoxicity of pentavalent vanadium.
- Vanadium compounds demonstrate potential as antitubulin agents, inducing aneuploidy in eukaryotic cells.