Chromosomal aberrations and sister-chromatid exchanges in workers exposed to styrene

Few studies exist about chromosomal damage in workers occupationally exposed to styrene. In the present study, chromosomal aberrations and SCEs were analyzed from cultures of peripheral lymphocytes of workers employed in 6 different reinforced-plastics industries with styrene air exposure levels ranging from 30 to 400 mg/mc. A control group was selected on the base of sex, age and smoking habit. We examined 50-h cultures (for chromosomal-aberrations) and 72-h cultures (for SCEs) for each individual.All workers exposed to styrene, as compared with controls, showed significantly increased frequencies of chromosomal aberrations, while SCEs were significantly increased at 4 of the 6 plants. High SCE values appeared with styrene air concentrations higher than 200 mg/mc.Apart from the possible presence and role of other interfering chemicals in the various plants, chromosomal aberrations seem to be more sensitive than SCEs for the detection of chromosomal damage caused by exposure to low doses of styrene.     

Chromosomal aberrations and sister-chromatid exchanges in workers exposed to styrene

Few studies exist about chromosomal damage in workers occupationally exposed to styrene. In the present study, chromosomal aberrations and SCEs were analyzed from cultures of peripheral lymphocytes of workers employed in 6 different reinforced-plastics industries with styrene air exposure levels ranging from 30 to 400 mg/mc. A control group was selected on the base of sex, age and smoking habit. We examined 50-h cultures (for chromosomal-aberrations) and 72-h cultures (for SCEs) for each individual. All workers exposed to styrene, as compared with controls, showed significantly increased frequencies of chromosomal aberrations, while SCEs were significantly increased at 4 of the 6 plants. High SCE values appeared with styrene air concentrations higher than 200 mg/mc. Apart from the possible presence and role of other interfering chemicals in the various plants, chromosomal aberrations seem to be more sensitive than SCEs for the detection of chromosomal damage caused by exposure to low doses of styrene.     

Cytogenetic monitoring of petrochemical workers

The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) in the peripheral blood lymphocytes of 360 persons, 180 workers in a petrochemical corporation and 180 appropriate controls, were studied. A significant increase in chromosomal aberrations and SCEs, compared to the control group, was observed in two sewage-treatment workshop workers; however, there were no significant differences between petrochemical workers from four workshops and a control group.     

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.     

Radiobiological effects of a low-energy ion beam on wheat

The radiobiological effects of a low-energy nitrogen ion (N⁺) beam on wheat were studied, particularly with regard to the induction of chromosome aberrations. The results demonstrated that the three test varieties showed different sensitivities to ion implantation, and a higher dose of ion implantation had a marked effect on the germination and survival rate of the seeds exposed. The germination rate and survival rate curve basically followed a similar trend in the same variety. Cytological analysis indicated that ion beams were effective in producing chromosome aberrations. The frequencies of mitotic or meiotic cells with chromosome aberrations increased linearly with increasing doses. The aberration types included, for example, acentric fragments, chromosome deletions, lagging chromosomes, chromosome bridges and micronuclei. In the root tip cells, aberrations chiefly consisted of acentric fragments and deletions. Chromosome bridges and lagging chromosomes were the main aberration phenomena observed in the pollen mother cells. The highest frequencies of root tip cells and pollen mother cells with chromosome aberrations were 15.2% and 39.8%, respectively. Changes in morphology and mutant were also observed in the plants derived from exposed seeds. Received: 10 April 2000 / Accepted: 10 October 2000     

Influence of sodium butyrate on the induction of radiation-induced chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary (CHO) cells.

CHO cells were pre-treated with sodium butyrate (SB) for 24 h and then X-irradiated in G1. Metaphases were scored for the induction of chromosomal aberrations and sister chromatid exchanges (SCEs). The data were compared with those obtained after irradiation of cells not pre-treated with SB and showed that SB has different effects on the endpoints examined. The frequencies of dicentric chromosomes were elevated and of small acentric rings (double minutes, DMs) reduced. These results are discussed to be a consequence of conformational changes in hyperacetylated chromatin which could lead to more interchromosomal and to less intrachromosomal exchanges. SB itself induces a few SCEs but suppresses the induction of SCEs by X-rays. We assume that a minor part of radiation induced SCEs are 'false' resulting from structural chromosomal aberrations, such as inversions, induced in G1. Inversions are the symmetrical counterparts of DMs. If inversions are suppressed by SB treatment to a similar extent as DMs a small reduction of SCEs by SB can be expected.     

Chromosomal aberrations and sister-chromatid exchanges in lymphocytes from coke oven workers

To test whether coke oven workers, an occupational group known to be at increased cancer risk, manifest increased peripheral blood chromosomal aberration frequencies, we obtained samples from a group of 30 steelworker volunteers, who had worked several years at coke oven jobs. Exposure estimates were made using measurements of work place atmospheric coal tar pitch volatiles and work histories. No statistically significant positive regression of chromosomal aberrations on exposure estimates was found. The data from the coke oven workers were also compared with the obtained concurrently and employing precisely the same laboratory protocol from a group of male Brookhaven National Laboratory employees. The coke oven workers as a group were found to have statistically significantly elevated frequencies of chromatid aberrations and of sister-chromatid exchanges.     

Analysis of streptozotocin-induced incomplete chromosome elements and excess acentric fragments in Chinese hamster cells using a telomeric PNA probe

Fluorescence in situ hybridization (FISH) with a telomeric peptide nucleic acid (PNA) probe was employed to analyze the induction of incomplete chromosome elements (ICE, i.e., unjoined or “open” chromosome elements with telomeric signal at only one end) and excess acentric fragments (i.e., in excess of fragments resulting from the formation of dicentric and ring chromosomes) by the methylating agent streptozotocin (STZ) in a Chinese hamster embryo (CHE) cell line. CHE cells were treated with 0–4 mM STZ and chromosomal aberrations were analyzed in the first mitosis after treatment using the telomeric probe. Centric (incomplete chromosomes) and acentric (terminal fragments) ICE were the only unstable chromosome-type aberrations induced by STZ in CHE cells. The induction of these aberrations exhibited a curvilinear concentration–response relationship. About 40% of the metaphases present in cell cultures treated with STZ contained one or more pairs of ICE. In STZ-treated cells, ICE were always observed as pairs consisting of an incomplete chromosome and a terminal fragment. Moreover, all of the excess acentric fragments induced by STZ were of terminal type. These results indicate that chromosomal incompleteness is a very common event following exposure to STZ and suggest that all of the excess acentric fragments induced by STZ originate from terminal deletions.     

Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. I. Correlation with chromosomal aberrations

We carried out a cross-sectional analysis of sister-chromatid exchanges (SCEs) and chromosomal aberrations induced by diepoxybutane (DEB) in lymphocyte cultures from 58 normal blood donors. DEB-induced SCE frequencies were measured in all subjects and chromosomal aberrations in 18. Analysis of variance was used to assess the contributions of exposure to organic solvents, age, smoking history, alcohol and coffee consumption, and red and white blood cell counts to variations in DEB-induced SCEs. In 10 individuals, the epoxide-detoxifying enzyme, glutathione (GSH)-S-transferase mu, was also measured. We observed a bimodal distribution of DEB-induced SCEs in the study population. Approx. 24% of the individuals were twice as sensitive to the induction of SCEs by DEB as the remaining 76%. Lymphocytes from persons sensitive to SCE induction by DEB contained a 4.4-fold increase in the number of DEB-induced chromatid deletions and exchanges. Within sensitive and resistant groups, significant interindividual variations in DEB-induced SCE frequencies were noted. Cigarette smoking was weakly associated with lower SCE frequencies within each group. Genetic deficiency in GSH-S-transferase mu was not correlated with increased sensitivity to SCE induction by DEB. Sensitivity to induction of SCEs by DEB can be rapidly determined and may be a marker of sensitivity to the induction of genotoxicity by certain classes of mutagens.     

Studies on the influence of photoreactivation on the frequencies of UV-induced chromosomal aberrations, sister-chromatid exchanges and pyrimidine dimers in chicken embryonic fibroblasts

Chicken embryonic fibroblasts, which possess photoreactivating enzyme were used to study the influence of photoreactivating light on the induction of pyrimidine dimers, sister-chromatid exchanges (SCEs) and chromosomal aberrations by 254 nm UV. While photoreactivation (PR) efficiently removed most of the induced dimers (75-95%), the frequencies of SCEs and chromosomal aberrations were reduced only by about 30-65%, in parallel experiments. Since pyrimidine dimers are the only photoreactivable photolesions known, the reduction in the frequencies of SCEs and chromosomal aberrations on PR has been interpreted as due to disappearance of pyrimidine dimers, implying that these lesions are the primary events responsible for the induction of the biological end points studied. The possible reasons for the lack of quantitative relationship between the frequencies of dimers and the frequencies of SCEs and chromosomal aberrations are discussed.     

Cytological characterization of repair-deficient CHO cell line 43-3B. I. Induction of chromosomal aberrations and sister-chromatid exchanges by UV and its modulation with 3-aminobenzamide

The induction of chromosomal aberrations and sister-chromatid exchanges (SCEs) by short-wave ultraviolet (UV) and X-irradiation was studied in Chinese hamster ovary (CHO) wild-type (WT) cells and one of its UV-hypersensitive mutants, 43-3B. The results indicate that CHO 43-3B show high levels of spontaneously occurring chromosomal aberrations and SCEs; these levels are, respectively, approximately 4 and 1.7 times those found in WT CHO. Treatment with UV produced a considerable delay in the cell-cycle progression of the mutant cells compared to the WT cells. Doses of UV that had no effect on WT cells, significantly induced chromosomal alterations in the mutant in a dose-dependent manner. An approximately 5-fold increase in the induced frequencies of SCEs was obtained in 43-3B cells after UV treatment. No synergistic effect was observed with UV irradiation and the inhibitor of poly(ADP-ribose) synthetase, 3-aminobenzamide (3AB), in either cell type. The frequency of SCEs in the mutant cell lines was lower than would be expected if the effects of UV and the inhibitor were additive. X-Ray alone in G1 and in combination with 3AB in G2 did not induce increased frequencies of chromosomal aberrations in mutant cells in comparison to the WT cells.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

The genotoxic risk of underground coal miners from Turkey

A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining.     

Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers

A cytogenetic analysis was performed on peripheral blood lymphocytes from 183 Chernobyl clean-up workers and 27 control individuals. Increased frequencies of chromosome aberrations were associated with exposure to radiation at Chernobyl, alcohol abuse and a history of recent influenza infection. However, only approximately 20% of Chernobyl clean-up workers had an increased frequency of dicentric and ring chromosomes. At the same time, an increased frequency of acentric fragments in lymphocytes of clean-up workers was characteristic. The use of multivitamins as dietary supplement significantly decreased the frequency of chromosome aberrations, especially of chromatid breaks. Rogue cells were found in lymphocytes of 28 clean-up workers and 3 control individuals. The appearance of rogue cells was associated with a recent history of acute respiratory disease (presumably caused by adenoviral infection) and, probably, alcohol abuse. Dicentric chromosomes in rogue cells were distributed according to a negative binomial distribution. Occurrence of rogue cells due to a perturbation of cell cycle control and abnormal apoptosis is suggested.     

Results of a cytogenetic study of populations with different radiation risks in the Semipalatinsk region

A cytogenetic study was conducted for the first time on human populations neighboring the Semipalatinsk nuclear test site (STS) and exposed to ionizing radiation for a long period of time. In populations with the extreme and maximum radiation risks, high frequencies of radiation-induced chromosomal markers, including acentric fragments (1.99 +/- 0.10 per 100 cells), dicentrics (0.23 +/- 0.01), ring chromosomes (0.38 +/- 0.14), and stable chromosomal aberrations (1.17 +/- 0.02), were found. These frequencies significantly exceeded those in control populations. The spectrum of chromosomal aberrations and the frequencies of the aberrations of different types in persons living in the areas with the highest radionuclide contamination confirmed the mutagenic effect of radiation on chromosomes in the human populations studied.     

Biological and chemical monitoring of occupational exposure to ethylene oxide

Studies were carried out on two populations occupationally exposed to ethylene oxide (EtO) using different physical and biological parameters. Blood samples were collected from 9 hospital workers (EI) and 15 factory workers (EII) engaged in sterilization of medical equipment with EtO and from matched controls (CI and CII). Average exposure levels during 4 months (the lifespan of erythrocytes) prior to blood sampling were estimated from levels of N-(2-hydroxyethyl)valine adducts in hemoglobin. They were significantly enhanced in EI and EII and corresponded to a 40-h time-weighted average of 0.025 ppm in EI and 5 ppm in EII. Exposures were usually received in bursts with EtO concentrations in air ranging from 22 to 72 ppm in EI and 14 to 400 ppm in EII. All samples were analyzed for HPRT mutants (MFs), chromosomal aberrations (CAs), micronuclei (MN) and SCEs. MFs were significantly enhanced by 60% in EII but not in EI. These results are the first demonstration of mutation induction in man by ethylene oxide. CAs were significantly enhanced in EI and EII by 130% and 260% respectively. MN were not enhanced in EI but significantly in EII(217%). The mean frequency of SCEs was significantly elevated by 20% in EI and by almost 100% in EII. SCE was the only parameter that allowed distinction between daily and occasionally exposed workers in EII. An interesting finding in exposed workers was the large increase of the percentage of cells with high frequencies of SCE (3–4 times in EI and 17-fold in EII).

The relative sensitivity of endpoints for detection of EtO exposure in the present investigation was in the following order: HOEtVal adducts > SCEs > chromosomal aberrations > micronuclei > HPRT mutants.     

Results of a Cytogenetic Study of Populations with Different Radiation Risks in the Semipalatinsk Region

A cytogenetic study was conducted for the first time on human populations neighboring the Semipalatinsk nuclear test site (STS) and exposed to ionizing radiation for a long period of time. In populations with the extreme and maximum radiation risks, high frequencies of radiation-induced chromosomal markers, including acentric fragments (1.99 ± 0.10 per 100 cells), dicentrics (0.23 ± 0.01), ring chromosomes (0.38 ± 0.14), and stable chromosomal aberrations (1.17 ± 0.02), were found. These frequencies significantly exceeded those in control populations. The spectrum of chromosomal aberrations and the frequencies of the aberrations of different types in persons living in the areas with the highest radionuclide contamination confirmed the mutagenic effect of radiation on chromosomes in the human populations studied.     

Chromosomal analysis in vinyl chloride exposed workers: Comparison of the standard technique with the sister-chromatid exchange technique

A group of 21 workers occupationally exposed to vinyl chloride and 6 controls were examined for the presence of chromosomal aberrations or sisterchromatid exchanges in their peripheral lymphocytes. These people comprised a second sampling from a group of exposed workers and controls first examined 18 months earlier. The vinyl chloride exposed workers showed levels of chromosomal aberrations elevated above those of the controls, but there was only a slight increase in sister-chromatid exchanges (per cell or per chromosome) and this increase was not statistically significant. Sister-chromatid exchanges (SCEs) were also examined from in vitro cultures of lymphocytes exposed in G₀/early G₁ and late G₁/early S phase to vinyl chloride, both with and without metabolic activation. There was no increase in SCEs in vitro without metabolic activation but there was a marked increase with metabolic activation and this increase was shown to be independent of cell-cylce phase. It thus was apparent that the small increases of SCEs in workers were not due to the inability of vinyl chloride to induce SCEs in human lymphocytes but were probably because of low exposures and SCE levels could have returned to normal relatively quickly after exposure. The present study suggested that the analysis of longer-living conventional chromosomal aberrations appeared to be a more sensitive monitor of exposure to vinyl chloride in exposed workers than the estimation of SCEs; however, it should be noted that in a 3rd sampling taken 24 months later the exposed workers had chromosomal aberration levels similar to the controls.     

Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin

Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.     

Constitutive heterochromatin polymorphism and chromosome damage in viral hepatitis

The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) were scored in relation to constitutive heterochromatin in 100 patients with viral hepatitis B, 100 patients with viral hepatitis A and 100 age- and sex-matched normal controls. 23.4%, 15% and 4% of the cells showed chromosomal aberrations in patients with hepatitis B, hepatitis A and normal controls respectively. Non-random involvement of chromosomal aberrations were also noted in chromosome 1 of patients with hepatitis B and A as compared to normal controls. The frequencies of SCEs (mean +/- S.D.) were found to be 10.40 +/- 2.83 in hepatitis B and 8.70 +/- 2.34 in hepatitis A. These values were significantly higher than the SCE frequency (mean +/- S.D.) of 5.88 +/- 2.25 observed in normal controls (P less than 0.001). The intra-chromosomal distribution of SCEs revealed a relatively increased incidence of SCEs in chromosome 1 of patients with hepatitis B and A as compared to normal controls. Analysis of constitutive heterochromatin polymorphism showed chromosome 1 qh+ to be the most frequent variant in patients with hepatitis B and A as compared to normal controls. The increased involvement of C-band variant 1 qh+ in patients with hepatitis B and A as compared to normal controls may indicate that extra heterochromatin offers additional sites for viral integration.