Antiproliferative and Genotoxic Action of an Underexploited Organoteluran Derivative on Sarcoma 180 Cells

Background: The search for novel metallic chemical compounds with toxicogenic effects have been of great importance for more efficient cancer treatment. Objective: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in S-180 cell line. Methods: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesis-block micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5 µM. Results: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20 µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5 µM, which is thought to avoid an aggressive immune response of the organism. Conclusion: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.

Modulating effect of Poincianella bracteosa (Tul.) L.P. Queiroz bark (Leguminosae) on DNA damage induced by doxorubicin on the somatic cells of Drosophila melanogaster wings

The aim of this study was to assess the genotoxic and antigenotoxic effects of Poincianella bracteosa bark aqueous extract on DNA damage induced by doxorubicin (DXR) a chemotherapeutic agent using SMART (Somatic Mutation and Recombination Test). The analysis was performed using the somatic mutation and recombination test in Drosophila melanogaster. Larvae from the standard and high-bioactivity crosses were chronically treated with four concentrations of P. bracteosa bark tea, alone and in association with DXR. The results revealed no mutagenic effect of bark extract for any of the concentrations tested. A modulating effect of aqueous extract in reducing the genotoxic action of DXR was observed for all concentrations tested in descendants of both crosses, but inhibition was more effective in those from the high-bioactive cross. The modulating effect observed may be associated with the presence of tannins and reducing sugars, as observed in phytochemical studies, since they are capable of capturing and stabilizing free radicals. Given the widespread use of P. bracteosa bark in folk medicine, further studies to elucidate the mechanism of action of these cellular compounds and with other experimental models would be useful to confirm that P. bracteosa extract is beneficial to human health.

Effect of estrogens and their metabolites genotoxicity on the pathogenesis and progression of estrogen-dependent breast cancer

Oncological diseases, due to the still increasing morbidity and mortality, are one of the main problems of modern medicine. Cancer of the mammary gland is the most common cancer among women around the world, and is the second cause of cancer deaths in this group, immediately after lung cancer. This kind of cancer belongs to an estrogen-dependent cancer, with proven associations with hormonal disorders in the body, occurring especially in the perimenopausal period and among women using hormone replacement therapy, as well as a result of the action of various xenobiotics that may interact with the estrogen receptor. Hormone steroids are widely used in medicine and their side effects are constantly discussed. The role of these compounds and their metabolites in maintaining hormonal balance is well understood, while many studies indicate the possible contribution of these steroids in the progression of the cancer process, especially in mammary gland tissue. Therefore, the genotoxic action of this group of compounds is still studied. Due to the limited number of scientific reports, the aim of this paper was to review and critically analyze data from the literature regarding the participation of estrogens (17β-estradiol) and their metabolites (2-methoxy estradiol, 4-hydroxy estradiol, 16α-hydroxyestrone) in the induction of carcinogenesis in mammary gland, in particular concerning the genotoxic activity of 17β-estradiol metabolites.

Bacterial DNA damage effectors in host cells

The microbiota has a significant, and sometimes decisive, effect on the host's homeostasis. The results of recent metagenomic studies confirm the importance of microbiota in maintaining health or its impact on the development of acute, chronic and neoplastic diseases. One of the important aspects of microbiota exposure is the ability of many bacterial species to induce mutations or modulate a mutation process in the cells of the host organism. This review summarizes the main experimental data revealing various mechanisms of genotoxic action of a bacterial microbiota, including direct damage to the DNA structure, induction of oxidative stress, delay in replication, and a decrease in repair efficiency. It is emphasized that bacteria use different strategies to ensure their own survival and replication, including. by suppressing the repair of host cell DNA, by promoting the survival of infected cells, despite the presence of DNA damage therein.

Testing the Potential Clastogenic/Cytotoxic Effects of Pesticide CALYPSO 480 SC

The detection of chromosomal damage serves as a tool for the verification of the genotoxic effects of chemical substancesin vitro. We used conventional cytogenetic analysis in order to test for the potential genotoxic action of the insecticide thiacloprid (the active ingredient in commercial preparation CALYPSO 480 SC). The test cultures of bovine lymphocytes obtained from the peripheral blood were incubated with the insecticide in concentrations of: 30, 120, 240 and 480 μg.ml−1for 24 and 48 hours. After 24 hours of incubation, we observed that the increasing concentrations resulted in a significant (P < 0.05; P < 0.01) increase in the frequency of DNA damage. Our experiments showed the presence of aberrations of a non-stable type (chromatid and chromosome breakage). The conventional chromosome analysis was supplemented with fluorescencein situhybridization for the detection of numeric and stable structural aberrations. Whole chromosome probes for bovine chromosomes 1, 5 and 7 (BTA 1, BTA 5 and BTA 7) were used in the experiments.

SOME PECULIARITIES OF THE ORGANISM’S RESPONSES TO A LONG-TERM INHALATION OF SILICA-CONTAINING SUBMICRON (PREDOMINANTLY, NANOSCALE) PARTICLES IN A REAL INDUSTRIAL AEROSOL

Female white rats were exposed in a «nose only» inhalation device to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica in a total concentration of 2.6±0.6 or 10.6±2.1 mg/m3, 4 h/day, 5 times a week, during up to 6 months. In an auxiliary experiment with a single-shot intratracheal instillation of these particles, it was shown that they induced a pulmonary cell response comparable with that when administrated a highly cytotoxic and fibrogenic standard quartz dust DQ12. However in a long-term inhalation test, the aerosol investigated proved to be of a very low systemic toxicity and fibrogenicity. This paradox may be explained by a low retention of SiO2 in lungs and other organs due to a relatively high in vivo solubility of those nanoparticles. Nevertheless their genotoxic action and transnasal penetration into the brain urge caution when assessing occupational or environmental hazard of that aerosol.