Cytogenetic analyses in peripheral lymphocytes of persons living in houses with increased levels of indoor radon concentrations

Published data concerning the effects of indoor radon exposure on the frequency of chromosome aberrations in peripheral lymphocytes of residents are contradictory. Possible reasons for this may be the low radon concentration in dwellings and/or the limited number of investigated persons. We therefore studied the relationship of domestic radon exposure and the occurrence of chromosome aberrations in peripheral lymphocytes in 61 persons living in houses with radon concentrations from 80 up to 13,000 Bq/m3. We analyzed 60,000 cells from fluorescence plus Giemsa (FPG)-stained slides. It could be clearly demonstrated that in groups of persons living in dwellings with indoor radon concentrations >200 Bq/m3 the number of cells containing dicentrics and/or centric rings (C(dic + cr)) (2.45 +/- 0.50 x 10(-3)) was significantly increased (p < 0.05) in comparison to the control level (1.03 +/- 0.15 x 10(-3)). However, there was no difference in the mean frequency of C(dic + cr) between the groups living in dwellings with higher radon concentrations. Using the fluorescence in situ hybridization (FISH) technique for the detection of translocations, we analyzed 23,315 cells in 16 persons of the highest exposed group (>5,000 Bq/m3). The observed frequency of translocations was 3.9 +/- 0.64 x 10(-3). In comparison to the control group (2.02 +/- 0.18 x 10(-3)), there was a slight but not statistically significant increase in the exposed group (P = 0.055). If, however, the age of the examined persons is taken into account, the values are significantly increased (P < 0.05) in the exposed persons older than 40 years in comparison to the age-matched controls. Since most of the translocations were found in stable cells, it is concluded that translocations are also induced in blood-forming tissue and are transmitted to peripheral blood.     

Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes

Chromosome damage and the spectrum of aberrations induced by low doses of γ-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/μm) in peripheral blood lymphocytes of four donors were studied. G₀-lymphocytes were exposed to 1–100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose–effect dependence was observed over the range of 1 to 50 cGy. At 1–7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose–effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena.     

Cytogenetic changes in peripheral blood lymphocytes of oncology patients

Analysis of home and foreign literature underlies the discussion of the significance of cytogenetic variations (frequency of aberrant cells and SCE-heteromorphism of C-chromatin and brittleness of chromosomes as indices of chromosome instability in oncological patients.     

Cytogenetic analysis of peripheral blood lymphocytes in workers exposed to benzene

In the present study, the method of cytogenetic analysis of peripheral blood lymphocytes was used to investigate 66 workers exposed to benzene, and 20 individuals selected from general population from the same locality, not exposed to particular mutagenic or carcinogenic agents (control group). Altogether, 8,600 metaphases were analysed. Frequencies of aberrant cells, including chromatide and chromosomal breaks, and chromatide and chromosomal exchanges, were scored in both groups. A very slight increase in aberrant cell frequencies (2.152% aberrant cells) was observed in the professional exposure group as compared to the control group (1.6% aberrant cells). Increased frequencies of aberrant cells were found in smokers of both the benzene-exposed and the control group. The differences were however not significant. In addition to cytogenetic examination, the workers underwent a general examination of their health condition (preventive examination). Benzene exposure seemed to have no injurious effect on the state of health of exposed workers. Biochemical and haematological tests gave normal values.     

Cytogenetic analysis of chromosomal aberrations of peripheral lymphocytes in workers occupationally exposed to nickel.

The authors carried out a cytogenetic examination of chromosomal aberrations of peripheral lymphocytes (100 cells evaluated in each sample) with simultaneous monitoring of the level of exposure by means of determination of nickel in the urine, serum and hair. The series included 21 workers occupationally exposed to nickel at two workshops producing NiO (6 persons) and NiSO4 (15 persons) in a chemical plant. At the same time a comparable control group, i.e., 19 workers of the same chemical plant but without any direct occupational nickel exposure (clerks, service men, etc.), were examined in the same way. In the exposed group chromosomal aberrations of peripheral lymphocytes were detected with an average value of 6.41 +/- 1.9% (range 2-14%); in the group producing NiO it was, on the average, 9.5 +/- 3.2% (range 7-14%) whereas in the NiSO4 production workers it was only 5.2 +/- 1.9% (range 2-10%). There was a dependence of chromosomal aberrations of peripheral lymphocytes on the exposure time and on the nickel content of the biological material. Significantly increased values (in contrast to the normal value of chromosomal aberrations of peripheral lymphocytes, up to 2%) were detected in the control group as well (average value of 4.05 +/- 2.27%, range 1-10%). The authors explain this fact by the nickel-polluted environment of the whole observed chemical plant.     

Cytogenetic effect of thaliblastine in a culture of human peripheral blood lymphocytes

The mutagenicity of thaliblastine (Bulgarian potential antitumor drug) was investigated in vitro in lymphocytes from healthy donors, and in vivo in lymphocytes of oncological patients after thaliblastine administration. No increase in the rate of chromosome aberrations was noted with increasing thaliblastine concentrations in vitro and in the course of therapy in vivo. Some polyploid metaphases were found in the lymphocytes of the patients treated with thaliblastine, as a result of the statmokinetic effect of the drug. Thaliblastine exerts extraordinarily slight mutagenic effect, as compared with other cytostatics.     

Cytogenetic analysis of peripheral blood lymphocytes in workers exposed to vinyl chloride

In the present study, the method of cytogenetic analysis of peripheral blood lymphocytes was used to examine 43 workers exposed to vinyl chloride monomer (average exposure 11.2 years) and 22 subjects selected from the same locality (control group). A total number of 8650 metaphases were analysed. All cytogenetic parameters examined were increased in the exposed group as compared to the control group and 3 parameters, chromatid breaks, percentage of aberrant cells and breaks per cell, were significantly increased (P less than 0.001).     

Cytogenetic study in peripheral blood lymphocytes from asthmatic patients receiving continued therapy with theophylline.

Possible cytogenetic effects of theophylline have been investigated in asthmatic patients undergoing continuous therapy with this drug. Sister-chromatid exchanges (SCE), chromosome aberrations (CA) and proliferating rate indices (PRI) were evaluated in cultured peripheral blood lymphocytes from patients receiving theophylline alone, theophylline plus inhaled beta 2 adrenergic drugs or theophylline in combination with beta 2 adrenergic agents and corticoids. Two samples from each individual were obtained in order to perform a prospective study: before the theophylline medication (sample A) and at a time after the beginning of treatment (sample B). After treatment (66.3 +/- 37.8 days), an increase in SCE was observed without modifications either in PRI or in CA. Patients receiving beta 2 adrenergics or beta 2 adrenergics plus glucocorticoids before and during theophylline treatment, did not respond differently than those on theophylline alone.     

Cytogenetic effects induced in vitro in human peripheral blood lymphocytes by neutrons. II. Relative biological effectiveness of neutrons having different energies]

Human lymphocytes were irradiated in vitro during Go stage by graded doses of thermal neutrons and neutrons having an average energy of 0.04; 0.09; 0.35; 0.85 and 14,7 MeV as well as by 60Co gamma rays, and RBE of neutrons relative to gamma-rays was calculated for the frequency of total and different types of aberrations. It was found that the RBE has the most value at the low doses and decreases when the exposition dose increases. 0.35 MeV neutrons have the maximum RBE in comparison with neutrons having other energies. When comparing the RBE values calculated for different types of chromosome aberrations, it was found out that dicentrics and dicentrics plus centric rings had more RBE than acentric aberrations (pair fragments and minutes).     

Cytogenetic effects of airborne particulate matter in human lymphocytes in vitro

City smog was collected in a heavily industrialized area and investigated for its ability to induce cytogenetic effects in human lymphocytes in vitro. Total extract of city smog was found to produce sister-chromatid exchanges and chromosomal aberrations in a dose-dependent manner. In addition cell-cycle delay was observed at higher concentrations of city smog extract. Results of cytogenetic testing are discussed with respect to cell-cycle kinetics.     

Cytogenetic effects of chloroquine in a culture of human lymphocytes]

Chloroquine added to human lymphocyte culture at the G1 stage had no influcence on the chromosome aberration level in the concentration of 15 mug/ml and suppressed the mitotic activity of the cells almost completely in the concentration of 60 and 100 mug/ml. At the G2 stage chloroquine in the concentration of 15 mug/ml had no cytogenetic effect and in the concentration of 100 mug/ml -- it increased the number of chromosome aberrations significantly.     

Cytogenetic analysis of peripheral blood lymphocytes of workers occupationally exposed to styrene

The genetic risk run by workers occupationally exposed to styrene vapors was assessed in two different plants A and B, using the cytogenetic analysis of peripheral blood lymphocytes. In plant A engaged in the manufacture of polystyrene vessels the mean styrene exposure level was found to range between 70 and 150 mg . m-3, in plant B manufacturing sports boats, plastic slides for children and plastic guard-stones it reached the level of about 200 mg . m-3. The rate of aberrant cells (AB.C.) found in plant A workers (N = 36) at the time of first sampling was 1.38% and the value of break/cell (B/C) ratio was 0.015; at the second sampling the rate of AB.C. was 1.41% and the B/C ratio was 0.014. The group of matched controls (N = 19) was found to have 1.26% of AB.C. and 0.014 breaks per cell. Plant B workers (N = 22) exhibited at the first sampling 1.72% of AB.C. and their value of B/C ratio was 0.018, the group of matched controls (N = 22) had 1.36% of AB.C and the B/C ratio 0.015; the respective values at the time of second sampling were 2.81% for AB.C. rate and 0.029 for B/C ratio in the exposed and 1.89% for AB.C. rate and 0.021 for B/C ratio in the control group. It is concluded that styrene exposure levels below 100 mg . m-3 do not pose any serious genetic risk for the exposed population groups. The variations found in the degree of chromosome injury by smoking habits, drug intake pattern, or sex were not statistically significant.     

Cytogenetic effects of low dose radiation with different LET in human peripheral blood lymphocytes and possible mechanisms of their realization

The induction of chromosome damage by the exposure to low doses of gamma-(60)Co and accelerated carbon ions 12C in peripheral blood lymphocytes of different donors was investigated. The complex nonlinear dose-effect dependence at the range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type aberration, which is typical to those spontaneously generated in the cell and believed not to be induced by the irradiation of unstimulated lymphocytes according to the classical theory of aberration formation. With the increasing dose the frequency of the aberrations decreases significantly, in some cases up to the control level. At the doses over 50-70 cGy the dose-effect curve becomes linear. The possible role of the oxidative stress, caused by radiation-induced increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon of hypersensitivity (HS) at low doses is discussed as well as cytoprotective mechanisms causing the increased radioresistance at higher doses.     

Cytogenetic effects of cyclophosphamide on human lymphocytes in vivo and in vitro

A comparative study of cytogenetic effects in human lymphocytes caused in vivo by cyclophosphamide (CP) after intravenous injection and in vitro by exposure of plasma of the same patients was carried out. It was found that the frequency of induced chromosome aberrations (CA) and sister-chromatid exchanges (SCE) increased linearly for SCE and exponentially for CA within the 'dose' of alkylating activity of CP metabolites. Parameters of 'cytogenetic effect-dose' in vivo and in vitro coincided. The intensity of cytogenetic effects varied between individuals.     

Cytogenetic analysis of peripheral blood lymphocytes in glass workers occupationally exposed to mineral oils

Chromosome aberration tests were carried out in a group of 31 pressed glass makers operating an automatic line of press-and-blow machines known to release mineral oil mists containing relatively high concentrations of the mutagenic chemicals belonging to a class of polycyclic aromatic hydrocarbons (PAH). The workers were exposed to the mineral oil aerosol levels that did not exceed the Czechoslovak maximum allowable concentration limit of 5 mg . m-1 of air. The tests revealed that the frequency of aberrant cells (% AB.C.) and the value of breaks per cell (B/C) ratio found in mineral oil-exposed workers were increased significantly, accounting for 4.65 +/- 0.29% AB.C. (0.0532 B/C) vs. 1.13 +/- 0.19% AB.C. (0.0113 B/C) seen in matching controls. Also, a higher rate of dicentrics, reciprocal translocations and cells with pulverization was observed in this group of glass workers. These finding are considered as evidence suggesting that these workers might experience an increased risk of genetic injury due to exposure to mineral oil mists.     

Mutagenicity studies on paracetamol in human volunteers. I. Cytogenetic analysis of peripheral lymphocytes and lipid peroxidation in plasma

The clastogenic activity of paracetamol (PC) was assayed on a group of 11 healthy volunteers. PC was administered in the form of tablets 3 x 1000 mg in the course of 8 h. Blood samples were taken 0, 24, 72 and 168 h after the first application of the drug. Each blood sample was used for the cytogenetic analysis of peripheral lymphocytes, for the measuring of the level of lipid peroxidation (LPO) and ascorbemia in plasma. After PC administration the frequency of aberrant cells (AB.C.) was increased to 2.77% AB.C. after 24 h vs. 1.68% at 0 h, and breaks per cell (B/C) to 0.0295 vs. 0.0182, respectively. If PC was applied simultaneously with ascorbic acid (AA), also in a dose of 3 x 1000 mg, an increased frequency of AB.C. was observed only after 72 h, of B/C after both 24 h and 72 h. No increase in LPO as determined by the thiobarbituric acid assay was seen after PC administration (1.02-1.10 nmole malondialdehyde (MDA)/ml plasma). The LPO level was increased 72 h after the simultaneous application of PC and AA (1.26 nmole MDA/ml). No effect of AA in terms of a decreased PC clastogenicity was observed.