ABSTRACT. Iron is the most important metallic chemical element on Earth. Poisoning caused by excessive iron in humans has been associated with pulmonary diseases including neoplasms caused by inhalation of iron oxides. The involvement of iron in neurodegenerative processes has already been described. DNA alterations are induced by iron and other chemical compounds containing this metal; however, the data are controversial and the mechanism by which iron induces mutagenesis remains unknown. This study assessed in vitro iron-induced cytotoxic and genotoxic responses in an astrocytic cell line. Short-and long-term cytotoxicity and genotoxicity were evaluated with the Cell Proliferation Kit II and micronucleus test, respectively. Results indicated that the highest concentration of iron sulfate tested was cytotoxic in long-term cytotoxic assays and increased micronucleus frequency in comparison to controls. The significant cytotoxicity observed here might be due to the intrinsic ability of iron to induce apoptosis and possible changes in cell cycle kinetics; the genotoxic effects are probably due to the oxidant properties of iron itself. This was the first study to investigate the induction of micronuclei by iron in central nervous system cells.
ABSTRACT. There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions.
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