Signaling and physiological activity of the NO-donating agent TNICthio in human blood lymphocytes, Jurkat and MCF7 cell lines.

Signaling and physiological activities of the crystalline tetranitrosyl iron complex with thiosulfate-a NO-donor (TNICthio) were first studied on human cells in conditions of mono and combined application of H2S and antioxidants. Comparative studies were performed on three cell lines: normal and leukemic T lymphocytes (Jurkat cells) and breast cancer MCF-7 cells (human breast adenocarcinoma). Also established was a high biological activity of TNICthio, as well as correlation between the levels of reactive oxygen species generation, the formation of double-strand breaks (DSB) in DNA and cell proliferation. The amount of DNA DSB repair in normal lymphocytes was tenfold higher than in leukemic cells. Inorganic H2S donor sodium hydrosulfide (NaHS) had insignificant effects on the production of reactive oxygen species and generation of DNA DSB in the cells of all the lines under study. However, H2S increased the tolerance of cells to the stress response after combined cell treatment with NO + H2S. 0.5 mM NO-donor and 0.1 mM antitumor antibiotic doxorubicin were equally effective generators of reactive oxygen species in MCF-7 cells; however, antiproliferative activity of the NO-donor, in this case, proved to be twice higher. The results obtained in this work may be promising for the prediction of pro- and antioxidant properties of the new NO and H2S donating compounds, as well as for the development of methods for complex anticancer therapy.

Effects of combined exposure to modeled radiation and gravitation factors of the interplanetary flight: Monkeys' cognitive functions and the content of monoamines and their metabolites; cytogenetic changes in peripheral blood lymphocytes.

In a study on primates (Macaca mulatta), neurobiological and radiobiological effects have been studied of the synchronous combined action of 7-day antiorthostatic hypokinesia and exposure of the monkeys' head first to γ-rays during 24 h and then to accelerated 12C ions. The neurobiological effects were evaluated by the cognitive functions which model the basic elements of operator activity and the concentration of monoamines and their metabolites in peripheral blood. The radiobiological effects were evaluated by the chromosomal aberration and DNA double-strand break (DSB) yield in peripheral blood lymphocytes. The results of the cognitive function research show that the typological features of the animals' higher nervous activity are the prevailing factor that determines changes in these functions. The monkey of the strong balanced type effectively retained its cognitive functions after the exposures, while in the weak unbalanced type animals these functions were impaired. These changes went along with a decrease in the concentration of monoamines and their metabolites and an increase in the DNA DSB and chromosomal aberration yield in lymphocytes.