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.

Delayed effects of accelerated heavy ions on the induction of HPRT mutations in V79 hamster cells.

Fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. Recently, priority has been given to the study of high-charge and high-energy (HZE) ions that comprise a substantial part of the galactic cosmic ray (GCR) spectra that would be encountered during long-term space flights. Moreover, predictions of the delayed genetic effects of high linear energy transfer (LET) exposure is becoming more important as heavy ion therapy use is increasing. This work focuses mainly on the basic research on the delayed effects of HZE ions on V79 Chinese hamster cells, with emphasis on the induction of HPRT mutations after prolonged expression times (ET). The research was conducted under various irradiation conditions with accelerated ions 18O (E=35.2MeV/n), 20Ne (E=47.7MeV/n and 51.8MeV/n), and 11B (E=32.4MeV/n), with LET in the range from 49 to 149 keV/µm and with 60Co γ-rays. The HPRT mutant fractions (MF) were detected in irradiated cells in regular intervals during every cell culture recultivation (every 3days) up to approximately 40days (70-80 generations) after irradiation. The MF maximum was reached at different ET depending on ionizing radiation characteristics. The position of the maximum was shifting towards longer ET with increasing LET. We speculate that the delayed mutations are created de novo and that they are the manifestation of genomic instability. Although the exact mechanisms involved in genomic instability initiation are yet to be identified, we hypothesize that differences in induction of delayed mutations by radiations with various LET values are related to variations in energy deposition along the particle track. A dose dependence of mutation yield is discussed as well.

Modeling nucleotide excision repair and its impact on UV-induced mutagenesis during SOS-response in bacterial cells.

A model of the UV-induced mutation process in Escherichia coli bacteria has been developed taking into account the whole sequence of molecular events starting from initial photo-damage and finishing with the fixation of point mutations. The wild-type phenotype bacterial cells are compared with UV-sensitive repair-deficient mutant cells. Attention is mainly paid to excision repair system functioning as regards induced mutagenesis.

Model of SOS-induced mutagenesis in bacteria Escherichia coli under ultraviolet irradiation.

A mathematical model of the mutation process in bacteria Escherichia coli induced by ultraviolet radiation is developed. Our model is based on the experimental data characterizing the main processes of the bacterial SOS response. Here we have modeled a whole sequence of the events leading to the fixation of the primary DNA lesion as a point mutation. A quantitative analysis of the key ways of the SOS mutagenesis was performed in terms of modern system biology. The dynamic changes of the basic SOS protein concentrations and the process of the translesion synthesis by the modified replication complex are described quantitatively. We have also demonstrated the applicability of the developed model to the description of the mutagenesis in individual genes. As an example, an estimation of the mutation frequency in E. coli's lacI gene is performed.