Effect of interferon on the yield of chromosome aberrations in cultured human lymphocytes irradiated with fast neutrons

A study was made of the influence of leucocytic interferon on the yield of chromosome aberrations in a human lymphocyte culture after irradiation of cells with fast neutrons (0.85 MeV) at the G0- and G1-stages. It was shown that in cells treated with interferon (50 UE/ml) prior to irradiation the total yield of aberrations and of some of their types was invariable as compared to the irradiated control.     

The effect of fluoride on chromosome aberration and sister-chromatid exchange frequencies in cultured human lymphocytes

Sodium fluoride, at concentrations of up to 60 times the level normally used in drinking water for the prevention of dental decay, was compared with 2 other inorganic salts for its ability to induce chromosome aberrations and sister-chromatid exchanges (SCE) in cultured human lymphocytes. No significant increases in the frequencies of aberrations of SCEs were found.     

Prediction of clonal chromosome aberration frequency in human blood lymphocytes

We recently conducted a large-scale screening for clonal aberrations among atomic bomb survivors and proposed a model for the gross clonal composition of blood lymphocytes. Here we show an application of the model indicating that the number, m,of clones detectable by cytogenetic methods in an individual is predictable by the equation m= (1.8 + 6.4FG) x FP x n/500, where FG represents the estimated translocation frequency in the 46 chromosome set, FP is the observed translocation frequency with FISH or other methods, and nis the number of cells examined. Application of the equation to the results of seven other reports gave close agreement between the observed and calculated numbers of clones. Since the model assumes that clonal expansion is ubiquitous, and any translocation can be the constituent of a clone detectable by cytogenetic means, the vast majority of observed clonal expansions of these somatic cells are likely the result of random-hit events that are not detrimental to human health. Furthermore, since our model can predict the majority of clonal aberrations among Chernobyl workers who were examined 5-6 years after irradiation, clonal expansion seems to occur primarily within a few years after exposure to radiation, most likely being coupled with the process of recovery from radiation-induced injury in the lymphoid and hematopoietic systems.     

Periodic variations of spontaneous chromosome aberration rate in human blood lymphocytes

Spontaneous chromosome aberration rate in human blood lymphocytes was studied using the data collected during 30 years. Seasonal variation was found. An absolute maximum of chromosome aberration rate was observed in winter and a local maximum, in summer. In spring and autumn, this value decreased. There was a statistically significant trend towards higher frequencies of aberrant metaphases during the period studied. A periodic pattern of changes in the chromosome aberration frequency was found. The data fitted a sinusoid with a period of 4.5 years.     

Biological indication and dosimetry of unstable chromosome aberration frequencies in human lymphocytes

Review is devoted to the problems of biological (cytogenetic) dosimetry and indication of degree of radiation lesions based on analysis of unstable chromosome aberrations in lymphocytes of human peripheral blood. Effects of radiation in low doses on human chromosomes and methodology of interpretation of the character of dose cytogenetic curves are discussed. Traditional cytogenetic analysis remains the basic one for monitoring in groups of people with accidental irradiation.     

Suppressive effect of novobiocin on the frequency of chromosome-type aberrations induced by ara C in the G1 phase of human lymphocytes

1-beta-D-Arabinofuranosylcytosine (ara C) induces chromosome-type aberrations in mammalian cells by inhibiting repair replication in the G1 phase. The effect of novobiocin, an inhibitor of prokaryotic gyrases, on G1 repair in human cells was studied cytogenetically using this characteristic of ara C. The experiment was based on the assumption that if novobiocin inhibits the relaxation of chromatin required prior to repair replication, it would reduce the frequency of chromosome-type aberrations in cells treated with a mutagen followed by posttreatment with ara C. It has also been shown that in lymphocytes ara C induces chromosome-type aberrations which were not caused by any induced DNA lesion, and that the frequency of these aberrations changes with the age of the blood donor. The effect of novobiocin on the frequency of chromosome-type aberrations induced by ara C in lymphocytes without mutagen pretreatment was also investigated for blood samples from donors of different ages. Human peripheral blood lymphocytes, which were either untreated of treated with 4-nitroquinoline-N-oxide (4NQO) or methyl methanesulfonate (MMS), were posttreated in their early G1 phase with ara C only or ara C and novobiocin. The resulting chromosome-type aberrations were observed in cells in their first mitoses, and a comparison was made between the frequency of aberrations occurring in the presence of novobiocin and in its absence. The results showed that novobiocin reduced the frequency of chromosome-type aberrations induced by ara C in both mutagen-pretreated and -non-pretreated cells, and that lymphocytes from younger donors were less sensitive to novobiocin. The present study demonstrated cytogenetically the existence of a novobiocin-sensitive process to induce chromosome recombination in G1 lymphocytes.     

The effect of age and low-dose irradiation on the chromosomal aberration frequency in human lymphocytes

The effect of age and of low-dose irradiation on the base level of chromosomal aberrations in lymphocytes was studied in two human groups: control one (128 people) and exposed in past to uncontrolled low-dose irradiation (283 people). In exposed group the frequencies of all types of chromosome aberrations were higher comparing to control group. For the investigation of the age response of the number of chromosomal aberrations three statistical approaches were used: correlation analysis of individual data, correlation analysis of mean frequencies of chromosomal aberrations for 10 years intervals, comparison of 3 age groups (young, middle age and old). In control group the significant increase of the level of chromosomal aberrations with age was found only when six 10-year intervals were analysed. In exposed group significant age increase of chromosomal aberration frequency (particularly due to double fragments) was observed with all 3 approaches. Low-dose irradiation of people is supposed to cause the functional defects of repair systems, controlling the level of genetic damages and they accumulate more intensive through age.     

Assessment of relative biological effectiveness of tritium using chromosome aberration frequency in human blood lymphocytes

The aim of this work is to determine Relative Biological Effectiveness (RBE) of tritium beta-irradiation using chromosome aberration frequency in peripheral blood lymphocytes after radiation exposure in vitro and in vivo. The results of the experimental estimation of tritium beta-irradiation RBE in comparison with 60Co gamma-irradiation using analysis of unstable chromosome aberration frequencies in peripheral blood lymphocytes in reference to concrete conditions of the investigation were presented. It was demonstrated that tritium beta-irradiation is in total more effective than gamma-irradiation up to 1 Gy. RBE of tritium beta-irradiation was determined as 2.2 at minimum doses and decreased at higher doses (1 Gy) up to 1.25. For the first time results of the comparative analysis of frequencies of stable chromosome aberrations in two groups of professional nuclear workers (town Sarov) exposed to chronic tritium beta- and gamma-irradiation in remote period were presented. The grater RBE of tritium beta-irradiation was demonstrated. It has been estimated as 2.5.     

Relation between cell cycle and yield of aberrations observed in irradiated human lymphocytes

The bromodeoxyuridine-Giemsa technique has been used to study systematically the incidence of cells in first or subsequent mitoses at different fixation times of human lymphocyte control cultures as well as the influence of ionizing radiations on cell kinetics. Second divisions appear (3%) in cultures harvested 48 h after initiation. In 72 h cultures 40% of the dividing cells are in second and 33% in third division. Administration of 200 rads of X-rays before PHA stimulation results in a mitotic delay but does not increase the incidence of SCE. The yield of dicentrics after an exposure to 200 rads was the same for all cells in first mitosis regardless of fixation time. These results demonstrate that there is no evidence for the existence of sensitive subpopulations that could be distinguished by the time of the first mitotic division following stimulation.     

The effect of mixed cultivation of lymphocytes irradiated at a dose of 1 Gy and non-irradiated lymphocytes on the frequency of chromosomal aberration

The mutual influence of irradiated (1 Gy) and non-irradiated cells was demonstrated on the model of the mixed culture oflymphocytes from opposite gender donors using chromosome aberrations (ChA) as an endpoint. The number of ChA in non-irradiated lymphocytes in mixed cultures with irradiated ones increased as compared to the corresponding monocultures. At the same time, the number of induced ChA decreased in the irradiated lymphocytes cultivated with non-irradiated ones.     

Influence of the bystander phenomenon on the chromosome aberration pattern in human lymphocytes induced by in vitro α-particle exposure

A recent publication on both chromosome-type and chromatid-type aberrations in lymphocytes of patients during treatment with radium-224 for ankylosing spondilitis has revived the question of whether the chromatid-type aberrations may be the consequence of factors released by irradiated cells. Therefore, the aim of the present study was to investigate the influence of such a bystander phenomenon on the chromosome aberration pattern of lymphocytes. Monolayers of human lymphocytes were irradiated with 1 Gy of α-particles from an americium-241 source in the absence or presence of whole blood, autologous plasma or culture medium. In the presence of any liquid covering the monolayer during irradiation, the chromatid-type aberrations were, contrary to expectation, elevated. Whereas the intercellular distribution of dicentrics was significantly overdispersed, the chromatid-type aberrations showed a regular dispersion. It can be concluded that the enhanced frequency of chromatid aberrations is the result of a damage signal or a bystander phenomenon released by irradiated cells.     

Estimation of relative biological effectiveness of tritium according to chromosome aberration frequency in human blood lymphocytes

The goal of this work was to determine the relative biological effectiveness (RBE) of tritium β-radiation according to the chromosome aberration frequency in the peripheral blood lymphocytes after in vitro and in vivo radiation exposures. The experimental RBE assessment of tritium β-radiation relative to ⁶⁰Co γ-radiation according to unstable chromosome aberration frequency in the peripheral blood lymphocytes under particular conditions is described. It has been demonstrated that tritium β-radiation is, in general, more effective in the dose range of up to 1 Gy, which is most pronounced at low doses. The RBE value of tritium β-radiation at minimum doses reached 2.2 and decreased at higher doses (1 Gy) to 1.25. The data on comparative analysis of the frequency of stable chromosome aberrations in the blood lymphocytes of professional nuclear workers (Sarov, Russia) after long-term chronic exposure to tritium β-radiation, as compared with γ-irradiation, are reported for the first time. The higher biological effectiveness of tritium β-radiation was demonstrated and was estimated as 2.5.     

Free radical scavenging in protection of human lymphocytes against chromosome aberration formation by gamma-ray irradiation.

Human peripheral blood lymphocytes were exposed to 300 rad gamma-rays, in the presence or absence of radical scavengers, and the change in the frequency of chromosome aberrations was analysed with attention directed to the protection by scavengers against the formation of primary damage leading to chromosome aberrations. The results showed that the damage involved in the formation of exchange-type aberrations was efficiently protected by scavengers, and about 60 per cent of them resulted from indirect action that could be abolished by alcohols. The SH-compounds afforded additional protection. The comparison of protective ability with reaction rates demonstrated that the indirect effect was due to the reaction of OH radicals possibly to DNA as a target molecule, and the involvement of H and eaq-was unlikely. In contrast to the exchange-type aberrations, terminal deletions were not significantly protected, suggesting that the damage leading to the terminal deletion differed in its nature from the leading to the exchange-type aberration.     

Effect of lipid hydroperoxides on the yield of chromosome aberrations in irradiated cells

The combined effect of linoleic acid hydroperoxide and gamma-radiation on Ehrlich ascites tumor cells was not additive with regard to the formation of chromosome aberrations. When cells were preincubated in the presence of a subliminal hydroperoxide dose of 2.10(-5) M the number of aberrant cells increased after irradiation.     

Acquired chromosome rearrangements in human lymphocytes: effect of aging

Summary A prospective study of structural rearrangements occurring in normal lymphocytes was carried out. For each of two newborns and four young and two old adults, about 1000 metaphases from 72-h and 120 from 48-h cultures were studied. The frequency of rearrangements between bands 7p14, 7q35, 14q11.2 or 14q12 and 14qter, which is on the average about 0.003, is higher in newborns (0.0043) than in adults (0.0024). Conversely, the rearrangements involving other bands, which have a frequency of 0.025 on the average, are more frequent in old adults (f=0.038) than in young adults (f=0.025) and newborns (f=0.013). The first type of rearrangement, which occurs in utero, may correspond to immunoglobulin and related gene rearrangements. The other rearrangements seem to accumulate progressively and may reflect exposure to mutagens. It is import to discriminate these two types of rearrangements when studying the effect of low doses of mutagens.     

Kinetics of proliferative processes induced by phytohemagglutinin in irradiated lymphocytes

The kinetics of the induced process of normal and exposed human lymphocytes to DNA synthesis and mitosis has been analyzed in detail. It was shown that the capacity of the exposed lymphocytes of repeated entering the phase of DNA synthesis was sharply decreased and the average length of the prereplicative period increased.