ABSTRACT
Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.
Subject(s)
Humans , Male , Female , Adult , Chromosome Aberrations/chemically induced , Insecticides/toxicity , Lymphocytes/drug effects , Rotenone/toxicity , Cell Cycle/drug effects , Cell Cycle/genetics , Cells, Cultured , DNA Damage/drug effects , Comet Assay/methods , Mitotic IndexABSTRACT
Hydroxyurea is considered an antineoplastic drug, which also plays an important role in the treatment of sickle cell anemia patients. We evaluated and compared the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal aberrations and mitotic index, respectively, as endpoints. In vitro short-term cultures of lymphocytes were exposed to several concentrations of this drug, at various cell cycle phases. There was a significant increase in the cytotoxicity of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle. Hydroxyurea did not significantly increase chromosome aberrations. There was an S-dependent cytotoxic effect of hydroxyurea, which is expected based on the known activity of hydroxyurea as an inhibitor of ribonucleotide reductase
Subject(s)
Humans , Chromosome Aberrations/chemically induced , Antineoplastic Agents/toxicity , Hydroxyurea/toxicity , Interphase/drug effects , Lymphocytes/drug effects , Analysis of Variance , Endpoint Determination , G1 Phase/drug effects , G1 Phase/genetics , /drug effects , /genetics , S Phase/drug effects , S Phase/genetics , Interphase/genetics , Mitotic Index , Mutagenicity Tests/methodsABSTRACT
The Canova Method (CM) is a homeopathic medicine indicated for the treatment of patients with cancer and for pathologies that involve a depressed immune system, such as AIDS. This product is composed of homeopathic dilutions of Aconitum napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom and Thuya occidentalis. It stimulates the immune system by activating macrophages. Activated macrophages stimulate the lymphocytes so that they increase their cytotoxic action in response to tumoral growth or infection. Given that the CM stimulates and accelerates the activity of macrophages and lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated with this homeopathic medication in vitro. Structural and numerical chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index was considered as a monitor for induced cellular toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following final concentrations of the medicinal composite CM: 4, 8 and 12. Treatments with the CM did not affect mitotic indexes, nor did they provoke chromosomal aberrations, when compared with untreated controls. There was no cytotoxicity or genotoxicity at the chromosomal level