Action of chronic irradiation on the cytogenetic damage of human lymphocyte culture.

The action of chronic irradiation (dose rate 2.9 Gy/day) on human lymphocyte culture was investigated. Whole blood was irradiated at 37 degrees C. Aliquots (0.2 ml) of whole blood were cultivated by the standard method. A medium containing phytohemagglutinin was added immediately after irradiation. All structural chromosome- and chromatid-type changes were recorded. The experimental data showed that the conditions of irradiation of lymphocytes affected neither the background level of chromosome damage nor their radiosensitivity. The obtained dose-response curve of chromosome aberrations was described by a linear regression, which then became a plateau. There is no statistically significant difference between the results for the low doses (10-50 cGy) of chronic and acute radiation.

Analysis of cytogenetic effects of the secondary radiation resulting from 70 GeV protons of Chinese hamster cells.

The cell culture of a Chinese hamster was irradiated on a Serpuchov proton synchrotron at a dose of 0.5-4 Gy and a dose rate of 1 Gy/min and by gamma-irradiation at dose 1-5 Gy and dose rate 1.2-1.4 Gy/min. The effect of radiation on the cell culture was judged from chromosomal aberrations in G2-stage of cell cycle and micronuclear test. The relative biological efficience of the secondary radiation was approximately 3. Modifying effect of caffeine on the cells irradiated by secondary radiation of synchrotron was not observed. In the presence of caffeine the effect of gamma-irradiation practically is increased up to the level observed upon secondary irradiation. This suggests that secondary radiation inhibits the repair of the cytogenetic damage.

[Effect of chronic neutron irradiation on fibroblast cell culture in Chinese hamster]. / Deistvie khronicheskogo neitronnogo oblucheniia na kulturu kletok fibroblastov kitaiskogo khomiachka.

The effect of monoenergy (30 Gev) neutron radiation on Chinese hamster fibroblasts has been studied by micronuclear test. It has been shown that in the range of doses up to 60 cGy RBE is equal to unity.

[Effect of chronic irradiation on cytogenetic mammalian cell injuries in culture]. / Vliianie khronicheskogo oblucheniia na tsitogeneticheskoe porazhenie kletok mlekopitaiushchikh v kulture.

The action of chronical irradiation on Chinese hamster fibroblasts and human peripheral blood lymphocytes was studied. The similar character of dose response for both types of cells and the absence of dose-rate effects at low doses were shown.

[Dependence of the cytogenetic adaptive response in the rat bone marrow cells on the dose of chronic gamma irradiation in vivo]. / Zavisimost' velichiny tsitogeneticheskogo adaptivnogo otveta v kletkakh kostnogo mozga krys ot dozy khronicheskogo gamma-oblucheniia in vivo.

The induction of chromosome aberrations in bone marrow cells of rats exposed to chronic gamma-irradiation and subsequently to acute gamma-irradiation was studied. Adult male rats were exposed ot 3-40 cGy (2.9 cGy/day) of chronic gamma-irradiation (adaptive dose) and subsequently to 4 or 6 Gy of gamma-rays (47 cGy/min, challenge dose). The yield of chromosome aberrations in marrow cells induced by adaptive and challenge dose was lower than the sum of the yields separately induced by chronic and acute gamma-irradiation. The most effective dose for induction of the adaptive response was 0.4 Gy.

[Induction of cytogenetic damage in Chinese hamster cells after combined exposure to low doses of gamma-radiation and various chemical and physical agents]. / Induktsiia tsitogeneticheskogo povrezhdeniia v kletkakh kitaiskogo khomiachka pri kombinirovannom vozdeistvii malykh doz gamma-radiatsii i razlichnykh khimicheskikh i fizicheskikh agentov.

Supersensitivity of Chinese hamster cells to low doses of gamma-radiation (dose range 5 to 50 cGy) was revealed by means of the cytokinesis-block micronucleus test. Treating these cells with caffeine (repair inhibitor) and mercaptoethylamine (radioprotector) and exposing them to secondary radiation emitted by protons with an energy of 70 GeV showed that this supersensitivity is associated with the absence of cytogenetic repair. When cells at the G2 phase received preliminary doses of 30 and 75 cGy before being irradiated at 150 cGy, the incidence of cytogenetic damage decreased, i.e., an adaptive cell response resulting from a radiation-induced mitotic delay was observed.

[Induction of cytogenetic damage to rat bone marrow cells by combined exposure to chronic and acute gamma radiation]. / Induktsiia tsitogeneticheskogo povrezhdenniia v kletkakh kostnogo mozga krys pri kombinirovannom vozdeistvii khronicheskogo i ostrogo gamma-oblucheniia.

The combined influence of various doses of chronic irradiation (0.029 Gy/day) followed by acute irradiation at doses of 4 and 6 Gy (0.47 Gy/min) on the frequency of chromosomal aberrations in rat bone-marrow cells was studied. A pronounced adaptive response was observed at all doses of chronic irradiation followed by acute irradiation.

[The role of ADP-ribosylation processes in the repair of cytogenetic damage in mammalian cells]. / Ob uchastii protsessov ADF-ribozilirovaniia v reparatsii tsitogeneticheskogo povrezhdeniia kletok mlekopitaiushchikh.

Nicotinamide (NA) was shown to increase the yield of chromosome aberrations in irradiated Chinese hamster cells. The effect was observed with all doses used (1-4 Gy) and in all phases of the cell cycle; it was maximum as cells transferred from S to G1 phase. The modification of radiation-induced aberrations was more pronounced in the chromatid deletions and in exchanges. The combined action of NA and caffeine showed a synergism. It is assumed that NA inhibits reparation in a different way than caffeine does.

[Distribution of DNA radiation damage throughout the cells and its comparison with cytogenetic injury]. / Izuchenie raspredeleniia radiatsionnykh povrezhdenii DNK po kletkam i ego sopostavlenie s tsitogeneticheskim povrezhdeniem.

The distribution of DNA lesions induced by irradiation of Chinese hamster fibroblast cells with different doses was determined by the cytochemical method in situ and compared with the number of cytogenetic damages caused by the same doses. The results obtained indicate that not all the DNA lesions but only those occurred in the structurally important chromosome sites initiate chromosome mutagenesis.

[Modeling, using nucleases, of the effect of radiation on Chinese hamster fibroblasts. On the role of single-stranded DNA breaks, induced by DNAase I, in the initiation of chromosome aberrations]. / Modelirovanie s pomoshch'iu nukleaz deistviia radiatsii na fibroblasty kitaiskogo khomiachika. O roli odnonitevykh razryvov DNK, indutsirovannykh DNKazoi I, v initsiatsii khromosomnykh narushenii.

DNAase I injected to Chinese hamster fibroblast cells resulted in the chromosome aberration induction at all stages of the cell cycle and death of cells. Comparison of the effects of DNAase I and gamma-radiation on Chinese hamster cells showed that with close values of the induced DNA breaks there were close values of the cytogenetic damage and the number of DNA damages per aberrant cell.

[Potential chromosome radiation damages in mammalian cells studied by chemical modification and premature condensation of the chromosomes]. / Issledovanie potentsial'nykh radiatsionnykh povrezhdenii khromosom v kletkakh mlekopitaiushchikh s pomoshch'iu khimicheskoi modifikatsii i prezhdevremennoi kondensatsii khromosom.

Chinese hamster cells in culture, exposed to a dose of 2 Gy during the G2 phase of the cell cycle, were used to compare the results obtained from investigations of chromosome lesions after chemical modification by caffeine (10(-3) and 10(-2) M) and after premature condensation of chromosomes. The data obtained exhibited a similarity not only in the total yield of aberrations (which was thrice as high as that in metaphases with the same radiation dose), but also in the frequency of aberrations of different types. On the basis of the data obtained the potential radiation-induced chromosome lesions could be quantitated.

[Nuclease-aided simulation of the action of radiation on Chinese hamster fibroblasts. The role of double-stranded DNA breaks induced by restrictases in initiating chromosomal disorders]. / Modelirovanie s pomoshch'iu nukleaz deistviia radiatsii na fibroblasty kitaiskogo khomiachka. O roli dvunitevykh razryvov DNK, indutsirovannykh restriktazami, v initsiatsii khromosomnykh narushenii.

Comparison was made between the effectiveness of restrictases inducing double-strand DNA breaks with blunt (Hae III and Eco RV) and cohesive (Hind III and Sal I) ends and that of gamma-radiation on the initiation of chromosome aberrations. The analysis of the spectrum of chromosome aberrations induced in the presence or absence of DNA repair inhibitors, as well as the study of the pattern of cell distribution by the number of DNA breaks per cell showed that the decisive role in the initiation of chromosome mutagenesis is played by the localization of the break in certain sequences of target DNA rather than the type of the break.

[Role of DNA damage in the formation of radiation damage to chromosomes]. / Rol' razlichnykh povrezhdenii DNK v formirovanii radiatsionnogo povrezhdeniia khromosom.

The data are reviewed on the role of various DNA lesions in the formation of structural damages to chromosomes. The concepts are developed that the molecular damages to nuclear DNA induce chromosome mutagenesis.

[The role of DNA repair processes in the repair of cytogenetic disorders. The participation of slow to repair DNA damage in the repair of cytogenetic disorders]. / Rol' protsessov reparatsii povrezhdenii DNK v reparatsii tsitogeneticheskikh narushenii. Uchastie medlennorepariruemykh povrezhdenii DNK v reparatsii tsitogeneticheskikh narushenii.

Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification.

[Role of the processes of repair of DNA damage in the repair of cytogenetic disorders. Participation of the repair of DNA single-strand breaks in the repair of cytogenetic disorders]. / Rol' protsessov reparatsii povrezhdenii DNK v reparatsii tsitogeneticheskikh narushenii. Uchastie reparatsii odnonitevykh razryvov DNK v reparatsii tsitogeneticheskikh narushenii.

A comparison was made between the results of the effect of poly(ADP-ribosylation) inhibitors (e.g. nicotinamide and 3-aminobenzamide) and a chromatin proteinase inhibitor, phenylmethylsulfonylfluoride, on the cytogenetic damages repair, by a micronucleus test and DNA repair in Chinese hamster fibroblasts. The values of the repair half-periods (5-7 min for the cytogenetic damages and 5 min for the rapidly repaired DNA damages) and a similar modifying effect with regard to radiation cytogenetic damages and kinetics of DNA damages repair were found to be close. This confirms the contribution of repair of DNA single-strand breaks in the initiation of structural damages to chromosomes.

[Proteinase participation in chromosome radiation damage. Research on the action of phenylmethylsulfonyl fluoride]. / Uchastie proteinaz v radiatsionnom povrezhdenii khromosom. Issledovanie deistviia fenilmetilsul'fonilftorida.

Phenylmethylsulfonyl fluoride, a chromatin proteinase inhibitor, caused a nearly twofold diminution of the cytogenetic injury and a twofold increase in the rate of DNA repair in gamma-irradiated (3-15 Gy) Chinese hamster fibroblasts. The effect of the inhibitor was mainly exhibited by a rapidly repaired (for 15-20 min) component of the cytogenetic damage. A simultaneous treatment with phenylmethylsulfonyl fluoride and nicotinamide did not influence the effect of the proteinase inhibitor under study. The results obtained are indicative of poly (ADP-ribosylation)-independent contribution of chromatin proteinases to radiation-induced chromosome mutagenesis.

[The protective action of a natural preparation of anthocyan (pelargonidin-3,5-diglucoside)]. / Issledovanie zashchitnogo deistviia prirodnogo preparata antotsiana (pelargonidin-3,5-digliukozid).

The effect of an anthocyan preparation isolated from flower petals of Pelargonium roseum and Rosa canina was studied in the Chinese hamster fibroblasts and Vicia faba seedlings in respect of cytogenetic damage and mouse survival. The pronounced radioprotective effect and the absence of the toxic effect were observed.

[The role of irreparable DNA damage in initiating chromosomal mutagenesis in Chinese hamster cells irradiated with gamma and secondary proton radiation with an energy of 70 GeV]. / O roli nerepariruemogo povrezhdeniia DNK v initsiatsii khromosomnogo mutageneza v kletkakh kitaiskogo khomiachka, obluchennykh gamma- i vtorichnym izlucheniem ot protonov s énergiei 70 GéV.

The study on the kinetics of DNA injury repair in Chinese hamster cells exposed to gamma and secondary proton radiation (70 GeV) has demonstrated the absence of distinctions in the kinetics of repair of rapidly repaired damages, a decreased rate of repair of slowly repaired lesions, and an increased residual irreparable damage induced by secondary radiation that reliably correlates with the RBE value estimated by the cytogenetic effect.

[Chromosome mutagenesis and cytogenetic monitoring]. / Problemy khromosomogo mutageneza i tsitogeneticheskogo monitoringa.

A model of formation of radiation-induced cytogenetic damage is proposed on the basis of our own and literature data. The model postulates that localization of DNA damage and repair process play an important role in the final effect.