Aberrations In Peripheral Lymphocytes Research Articles

Cytogenetic and epigenetic aberrations in peripheral lymphocytes of northwest Arkansas Marshallese

Purpose Nuclear weapons testing in the northern Marshall Islands between 1946 and 1958 resulted in ionizing radiation (IR) exposure of the thousands of Marshallese. Furthermore, numerous islands were contaminated by radioactive fallout. Significant increases in cancer and metabolic syndrome incidences have been reported among Marshallese, and potential for further increases looms due to the latency of radiation-induced health effects. The purpose of this study was to investigate the genetic and epigenetic effects of exposure to IR that could be associated with radiation-induced disease among the Northwest Arkansas (NWA) Marshallese. Materials and Methods We performed analysis of chromosomal aberrations and DNA methylation based on residential and exposure history of NWA Marshallese. Results Analysis of chromosomal aberrations demonstrated higher incidence of genetic rearrangements in women with self-reported history of radiation exposure (95% CI: 0.10, 1.22; p=.022). Further clustering of study participants based on their residential history demonstrated that participants who spent substantial amounts of time (≥6 months) in the northern atolls (thus, in the proximity of nuclear tests) before 1980 had more chromosomal aberrations than their peers who lived only in the southern atolls (95% CI: 0.08, −0.95; p=.021), and that this difference was driven by women. A relationship between the time spent in the northern atolls and increase in chromosomal aberrations was observed: 0.31 increase in chromosomal aberrations for every 10 years spent at northern atolls (95% CI: 0.06, 0.57; p=.020). Finally, significant inverse correlations between the chromosomal aberrations and the extent of DNA methylation of four LINE-1 elements L1PA2, L1PA16, L1PREC1, and L1P4B were identified. Conclusions The results of this study provide first evidence of the presence of stable genetic and epigenetic rearrangements in peripheral lymphocytes of NWA Marshallese and warrant further studies to analyze the role of radiation exposure in health disparities experienced by this Pacific Island nation.

Genotoxic effect of simultaneous therapeutic exposure to polycyclic aromatic hydrocarbons and UV radiation.

Polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) represent genotoxic factors that commonly occur in the living and working environment. The dermal form of exposure represents a significant part of the total load of dangerous chemical and physical environmental factors to which an organism is subjected. However, simultaneous dermal exposures to PAHs (pharmaceutical crude coal tar [CCT]) and UV (UVA and UVB) also have therapeutic uses. A typical example is Goeckerman therapy (GT) for psoriasis. The question of the therapeutic efficacy of GT and the related level of genotoxic danger is still under discussion. The aim of the present study was to compare four GT variants (G1-G4) in terms of efficacy and acceptable genotoxic hazard. Efficacy was expressed by the psoriasis area of severity index (PASI) score, genotoxic hazard by chromosomal aberration in peripheral lymphocytes. The lowest risk of genotoxic hazard and the lowest efficiency was observed in G1 variant (3% of the CCT and UVA + UVB). The efficacy of G2 (4% CCT and UVA + UVB), G3 (4% CCT and UVB), and G4 variants (5% CCT and UVA + UVB) was comparable. The highest risk of genotoxic hazard was found in the G3 variant. In the terms of sufficient efficacy and acceptable genotoxic hazard, a combination of 4% or 5% of CCT and UVA and UVB seems to be acceptable (variants G2 and G4).

Cardiac catheterization procedures in children with congenital heart disease: Increased chromosomal aberrations in peripheral lymphocytes

Cardiac catheterization procedures are performed on about 20,000 children with congenital heart disease (CHD) annually in China. The procedure, which involves exposure to ionizing radiation, causes DNA damage and may lead to increased cancer risk. We have studied chromosomal aberrations (CA) in peripheral lymphocytes of CHD children. CA frequencies were assessed in an interventional group of 70 children who underwent cardiac catheterization and a control group of 51 children receiving open-heart surgery. Total CA and all chromosome-type aberrations were higher in the exposed children than in the control group. With respect to the type of septal defect, the translocation frequency was higher in patients with ventricular rather than atrial defects. Cardiac catheterization procedures increase CA frequencies and may also increase the risk of cancer.

Methods of Classical and Molecular Cytogenetics Suitable for Biodosimetry of Persons with Professional Exposure to Carcinogens.

People in the health professions and other occupations are frequently exposed to carcinogens, including chemicals, cytostatic agents, and ionizing radiation with carcinogenic potential. These individuals require monitoring of their exposure, as well as biomonitoring for cytogenetic alterations. Classical and molecular cytogenetic methods can establish functional remedial measures, while preventing the emergence of malignant tumors as an occupational disease. This article presents the main principles, advantages, and limitations of classical cytogenetic and modern molecular cytogenetic methods. These include conventional cytogenetic analysis of chromosomal aberrations in peripheral lymphocytes of individuals exposed to chemical carcinogens and examination of sister chromatids and micronuclei after exposure to ionizing radiation. More recent methods include radioactive and fluorescence in situ hybridization, colour variants of the latter, comparative gene hybridization, spectral karyotyping, and the latest microchip methods. Molecular cytogenetic methods make possible the refinement of methods used in the biomonitoring of chemicals and radiation. Their benefits include higher speed, automation of some processes, high sensitivity, focus on stable genetic changes capable of triggering the carcinogenesis process, and the possibility of determining deviations in non-dividing cells. Their disadvantages to date include lack of analysis of large numbers of individuals undergoing preventive examinations, undetermined norms or limit values for exposed individuals and work teams, and higher costs of examination. This work was supported from the program project of the Agency for Health Research of the Czech Republic with registration number P09-15-33968A with the fi nancial support of the Ministry of Health. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 15. 10. 2018 Accepted: 4. 7. 2019.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process

BackgroundUltraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). ObjectiveTo determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). MethodsThe study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. ResultsIntensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). ConclusionDermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

Elevated levels of circulating biomarkers of cell death (nucleosomes) in the patients with plaque psoriasis treated with the Goeckerman regimen.

Nucleosomes are complexes that are formed during apoptosis. Psoriasis is a chronic skin disease characterized by keratinocyte hyperproliferation and anti-apoptotic features. Presented study was focused to expression of circulating biomarkers of cell death (circulating nucleosomes, CN) during Goeckerman therapy of psoriasis (UV, PAHs). In a group of patients with psoriasis (19), treated with Goeckerman regimen (GR), we evaluated their level of CN, level of chromosomal aberration in peripheral lymphocytes (CA), level of urinary 1-hydroxypyrene (1-OHP) and their value of Psoriasis Area and Severity Index (PASI). Following the treatment, the serum level of CN and urinary level of 1-OHP (p<0.05) were significantly increased (p<0.01). We found significant correlation between CN and urinary level of 1-OHP after GR (r=0.57; p<0.05). Immediately after the treatment we found significantly increased total numbers of abnormal chromosomes (ABB; p<0.01) and structurally abnormal chromosomes (SAB; p<0.05). We found slightly (but statistically significant) elevated level of circulating biomarkers of cell death (nucleosomes) in patients with plaque psoriasis treated with GR (PAHs, UV radiation). We suppose that elevated level of CN is a result of combination of the positive effects of GR and its weak genotoxic effect (mainly PAHs). Conclusions are supported by significant correlation between CN and urinary level of 1-OHP after GR and significantly elevated level of CA after GR (Tab. 2, Fig. 1, Ref. 28).

Oxidative damage to nucleic acids and benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA adducts and chromosomal aberration in children with psoriasis repeatedly exposed to crude coal tar ointment and UV radiation.

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

Analysis of Sheep Lymphocyte Chromosomal Aberrations after Exposition to Chlortetracycline

Tetracyclines are broad spectrum antibiotics and one type of various their compounds—chlortetracycline has been successfully used for our cytogenetic studies. We have selected for these studies the chromosomal assay because it is wellknown cytogenetic biomarker, which has been used to assess DNA damage at the chromosomal level. We analyzed the chromosomal aberrations and mitotic index in peripheral lymphocytes of sheep exposed by chlortetracycline chloride in pure tap water. To the food of the experimental group of animals (à n = 6) were added also 0.35 gof preparation Aureovit12 C80 plv. a. u. v. per kg b. w. and day (i.e. 168 mg of chlortetracycline hydrochloride/kg b. w.) daily in food. The frequencies of aberrant cells (ABC) in the experimental and control groups of sheep were stated to differ significantly (P = 0.001). In experimental group, chromatid breaks were the dominant type of chromosomal aberrations. No statistical differences in mitotic index values were found in the both groups (P > 0.05). Increased frequencies of chromosome aberrations in peripheral lymphocytes of sheep exposed by chlortetracycline in food, suggested a potential hazard which needs the attention from the viewpoint of human and animal health. This knowledge is useful for all, for the human and veterinary medicine, as well as for the aquaculture. Many of these chlortetracycline substances for their environmental persistence and chemical unstability are present in the environment for various periods, and as a result, they are responsible for several effects on human and animal health through food chain.

Urinary mutagenicity and genotoxic risk in children with psoriasis after therapeutic exposure to polycyclic aromatic hydrocarbons and ultraviolet radiation

The Goeckerman regimen (GR) for the treatment of psoriasis comprises dermal application of crude coal tar (polycyclic aromatic hydrocarbons, PAHs) and exposure to ultraviolet radiation (UVR). PAHs and UVR are mutagenic and carcinogenic agents. We evaluated dermal absorption of PAHs as well as the mutagenic and genotoxic effects of GR in 16 children with psoriasis, by determining levels of 1-hydroxypyrene (1-OHP), 1-,2-,3-,4-hydroxyphenanthrene, (1-OHPhe, 2-OHPhe, 3-OHPhe, and 4-OHPhe), urinary mutagenicity ( Salmonella mutagenicity assay, Ames test) and numbers of chromosomal aberrations in peripheral lymphocytes (CA), in urine and/or blood, before and after GR. The Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GR. Compared with pre-treatment levels, there were significant increases in urinary concentrations of 1-OHP ( p < 0.001), 1-OHPhe ( p < 0.001), 2-OHPhe ( p < 0.001), 3-OHPhe ( p < 0.001), and 4-OHPhe ( p < 0.01), indicating a high degree of dermal absorption of PAHs. There were also significantly increased numbers of revertants in the Ames test in two different strains (YG1041−S9, p < 0.01; YG1041+S9, p < 0.001; TA98+S9, p < 0.01), which demonstrates urinary mutagenicity. We also found a significant increase in the number of CA ( p < 0.001) and significantly decreased number of CA ( p < 0.01) at 81 days post-treatment, suggesting that GR has a temporary genotoxic effect. The PASI scores were significantly decreased after GR ( p < 0.001), confirming the clinical benefit of GR. In conclusion, our results demonstrate mutagenic and temporary genotoxic effects of GR in the group of 16 treated child patients.

Frequency of chromosomal aberrations in peripheral lymphocytes of tannery workers in Brazil

To evaluate the incidence of chromosomal aberrations (CA) in peripheral lymphocytes of workers chronically exposed to chemical hazards in a tannery in Franca, São Paulo, Brazil. The exposed group consisted of 10 male workers employed in the same tannery. The duration of work in the tannery ranged from 5 months to 14 years. The control group consisted of 10 males without a history of exposure to chemicals or other potentially genotoxic substances. A total of 100 well-spread metaphases were analyzed per subject. The frequency of CA was higher in the exposed group than in the control group. Smoking had a significant effect on the frequency of CA in both the control and the exposed groups. Chronic occupational exposure of tannery workers represents a relevant risk factor for the development of diseases associated with genetic damage.

Arsenic Methylation, Urinary Arsenic Metabolites and Human Diseases: Current Perspective

Arsenic can cause cancerous and non-cancerous human diseases. Inorganic arsenic from drinking water is the most common source of human exposure. Pentavalent arsenate can be reduced to trivalent arsenite in the blood, which is taken up mainly in the liver and metabolized by a sequence of reduction and oxidative methylation. A proportion of the inorganic arsenicals together with methylated metabolites are excreted in urine. Analyses of the urinary arsenic profile can give a hint to the methylation capacity of exposed individuals. All studies evaluating the association between urinary arsenic profiles and human diseases nowadays measure mainly the inorganic arsenate and arsenite and the two organic forms of methylated metabolites: the pentavalent form of monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV). A review of the current literature suggests that reduced methylation capacity with increased MMAV percentage, decreased DMAV percentage, or decreased DMAV/MMAV is associated with skin lesions, skin cancer, bladder cancer, peripheral vascular disease, muscle cramps and structural chromosome aberrations in peripheral lymphocytes obtained from exposed subjects. The detection of the recently identified more toxic trivalent forms of methylated metabolites in urine awaits further confirmation.

Chromosomal aberrations in peripheral lymphocytes from male native miners working in the Peruvian Andes

We analyzed the frequency of chromosomal aberrations in peripheral lymphocytes from underground miners from the Casapalca (n = 8, mean age = 45 y, range = 36 y to 55 y) and Bellavista (n = 8, mean age = 28 y, range 23 y to 34 y) high-altitude mining camps in the Peruvian Andes. This population was occupationally exposed to heavy metals such as lead and zinc as well as diesel emission particles, organic solvents and mine dust. The control groups consisted of individuals from a high altitude farming community in the Peruvian village of Tinco (n = 8, mean age = 37 y, range = 25 y to 52 y) and the sea level city of Lima (n = 14, mean age = 26 y, range = 20 y to 35 y). All individuals were male native Peruvians. A significantly higher incidence (1.88%, p < 0.05) of chromosomal aberrations (chromatid deletions and breaks, chromosome breaks and acentric fragments) were detected in lymphocytes from miners at the Casapalca camp as compared to miners from the Bellavista camp (0.5%, chromatid deletions and acentric fragments only) and the Lima sea level (0.07%, chromatid deletions only) and Tinco high altitude (no aberrations) controls. These results suggest that male native Peruvians occupationally exposed to underground mining activity have an increased frequency of chromosomal aberrations, which could be related to both age and exposure time. The increased chromosomal damage observed in the mining populations studied may be attributable to the complex mixture of genotoxic agents to which the miners may have been exposed.

Exposure assessment of benzene in Thai workers, DNA-repair capacity and influence of genetic polymorphisms

Exposure to benzene can cause DNA damage and the subsequent development of cancer. In this study, study subjects were 31 laboratory workers at a petrochemical factory and 31 gasoline service attendants. Control subjects were 34 workers from a mail sorting service center. Occupational exposures to benzene were assessed using biomarkers of exposure in blood and urine. Induction of DNA-repair capacity was assessed as a biomarker of early effect. The effects of polymorphisms in a metabolizing gene ( CYP2E1), in detoxification genes ( NQO1 and GSTT1), and in a DNA-repair gene ( XRCC1, codon 399) on biomarker levels were evaluated. The mean individual benzene exposure of laboratory workers (24.40 ± 5.82 ppb) and that of gasoline service attendants (112.41 ± 13.92 ppb) were significantly higher than in controls (1.39 ± 0.17 ppb, p < 0.001). Blood benzene levels of laboratory workers (169.12 ± 30.60 ppt) and gasoline service attendants (483.46 ± 59.62 ppt) were significantly higher than those of the controls (43.30 ± 4.89 ppt, p < 0.001). Trans, trans-muconic acid levels in post-shift urine samples collected from laboratory workers (0.14 ± 0.02 mg/g creatinine) and gasoline service attendants (0.20 ± 0.02 mg/g creatinine) were significantly higher than in urine samples of controls (0.04 ± 0.01 mg/g creatinine, p < 0.001). The level of benzene exposure was correlated with blood benzene levels ( R 2 = 0.65, p < 0.01) and post-shift urinary trans, trans-muconic acid concentrations ( R 2 = 0.49, p < 0.01). As a biomarker of early effect, DNA-repair capacity was assessed by use of the cytogenetic challenge assay, i.e., chromosomal aberrations in peripheral lymphocytes were assessed after challenging blood cultures with 1 Gy gamma radiation. A significantly lower DNA-repair capacity – determined as dicentrics in laboratory workers (0.17 per metaphase cell) and in gasoline service attendants (0.19 per metaphase cell) compared with controls (0.12 per metaphase cell, p < 0.001) – was observed. The frequency of deletions in laboratory workers (0.22 per metaphase cell) and gasoline service attendants (0.39 per metaphase cell) were significantly higher than in control workers (0.16 per metaphase cell, p < 0.01 and p < 0.001, respectively). An increase in radiation-induced dicentrics and deletions indicate a lower DNA-repair capacity in benzene-exposed workers. The influence of genetic polymorphisms on the biomarkers was assessed. Benzene-exposed workers who carried CYP2E1*1/*5 or *5/*5 genotypes excreted slightly higher levels of trans, trans-muconic acid than workers who carried the CYP2E1*1/*1 genotype. In this study, NQO1 and GSTT1 genotypes did not have any effect on the levels of trans, trans-muconic acid. In the case of XRCC1, laboratory workers with 399Arg/Gln or Gln/Gln had a lower DNA-repair capacity – measured as radiation-induced frequency of dicentrics and deletions – than those with the 399Arg/Arg genotype ( p < 0.01). Our results show that biomarkers of internal dose and early biological effect in people occupationally exposed to benzene are influenced by genetic polymorphisms in susceptibility genes.

Induction of chromatid-type aberrations in peripheral lymphocytes of hospital workers exposed to very low doses of radiation

Radiological personnel represent workers exposed to low cumulative doses of radiation. As their surveillance is generally based on physical dosimetry, there is little or inconclusive information on biological effects due to radiation exposure at these doses. We aimed to explore the extent of chromosomal damage in circulating lymphocytes of hospital workers (technicians, nurses and physicians) chronically exposed to a very low level of radiation using conventional and molecular cytogenetic analyses (chromosome painting with chromosomes #2, #3 and #10 as probe cocktail). Compared with controls, exposed workers displayed a significant increase in the frequency of aberrant lymphocytes (1.26 ± 0.11/100 cells versus 1.63 ± 0.17/100 cells). In particular, exposed technicians showed significantly higher mean values than nurses or physicians (3.68 ± 1.17/100 cells versus 1.36 ± 0.18/100 cells and 1.36 ± 0.09/100 cells, respectively). Interestingly, we found that the chromosomal damage was prevalently expressed as chromatid-type aberrations. Chromosome painting indicated that the frequency of chromosome rearrangements (CR; translocations and dicentrics pooled together) was approximately comparable between radiological workers and the control group. Moreover, we did not detect any significant difference due to radiation exposure when CR rates were considered separately for each of the three chromosomes in the probe cocktail.

Genotoxic effect of Goeckerman regimen of psoriasis

Goeckerman regimen (GR) of psoriasis includes daily dermal application of crude coal tar (CCT) and dermal exposure to UV-A and UV-B radiation. Observed group consisted of 23 patients with psoriasis treated by GR. Therapeutic ointment contained 5% of CCT. The level of psoriasis area and severity index was significantly decreased after GR (P < 0.001) and confirms high efficiency of GR. High levels of selected metabolites of pyrene and phenanthrene indicated high level of dermal penetration. We found significantly increased urinary mutagenicity in samples collected in the middle and in the end of GR (TA98+S9, P < 0.01; YG1041-S9, P < 0.001; YG1041+S9, P < 0.001). Significant increasing of chromosomal aberrations in peripheral lymphocytes (CA) in blood samples collected in the end of GR (P < 0.001) and consecutive decreasing of CA in 78th day after the end of GR has been observed. Almost all results indicated that the patients could be endangered by a peak genotoxic exposure. Nevertheless, the genotoxic effect does not seem to be long lasting. Despite conflicting results from cancer epidemiological studies, it is evident that single GR can contribute to the total load of environmental mutagens in a group of treated patients.

Chromosomal aberrations in peripheral lymphocytes of patients treated with radium-224 for ankylosing spondylitis

The aim of this study was to investigate the in vivo frequency of chromosomal aberrations (primarily dicentric chromosomes and chromatid breaks) potentially induced by (224)Ra alpha-radiation in peripheral lymphocytes. The study was designed to serve as a cytogenetic analysis along with the therapeutic procedure of ankylosing spondylitis patients who were undergoing a treatment with (224)Ra-chloride. The total administered activity was 10 MBq, and the treatment followed a schedule of 10 i.v. injections per week, each with a dose of 1 MBq of (224)Ra. The calculation of absorbed doses delivered to the blood used the models suggested by the ICRP and yielded a value of 4.7 mGy/MBq. The frequency of chromosomal aberrations observed during the course of therapy was related to the blood dose. The frequency of dicentric chromosomes induced in vivo was found to agree well with the corresponding value of dicentrics induced in vitro. However--given that peripheral lymphocytes are in the cell cycle's G(0) stage--an unexpected increase with dose in the yield of chromatid breaks was observed, with about 95% of them occurring in cells without any other chromosome-type aberrations. Reasons for the production of chromatid breaks are discussed.

Chromosome aberrations in peripheral lymphocytes of individuals living in dwellings with an increased level of indoor radon concentrations

Sixty one individuals living in dwellings with increased indoor radon concentrations (80–13,000 Bq/m 3) were investigated cytogenetically. The frequency of dicentric chromosomes (dic) and centric rings (cr) showed a dependency on the time integrated radon concentration from ≤1000 to 10,000 Bq/m 3·y. At values higher than 10,000 Bq/m 3·y, the frequency remained on the same level. The frequency of translocations was determined in 16 persons living in houses with radon concentrations >5000 Bq/m 3. In persons older than 40 years, a significantly increased frequency was observed in comparison to the age-matched controls ( p<0.05). 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. There is good agreement between physically calculated doses, according to ICRP and BEIR VI, and biologically calculated doses for blood and bone marrow.

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 × 10^–3) was significantly increased (p < 0.05) in comparison to the control level (1.03 ± 0.15 × 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 × 10^–3. In comparison to the control group (2.02 ± 0.18 × 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.

Spectrum of chromosomal aberrations in peripheral lymphocytes of hospital workers occupationally exposed to low doses of ionizing radiation

Chromosome aberrations frequency was estimated in peripheral lymphocytes from hospital workers occupationally exposed to low levels of ionizing radiation and controls. Chromosome aberrations yield was analyzed by considering the effects of dose equivalent of ionizing radiation over time, and of confounding factors, such as age, gender and smoking status. Frequencies of aberrant cells and chromosome breaks were higher in exposed workers than in controls ( P=0.007, and P=0.001, respectively). Seven dicentric aberrations were detected in the exposed group and only three in controls, but the mean frequencies were not significantly different. The dose equivalent to whole body of ionizing radiation (Hwb) did appear to influence the spectrum of chromosomal aberrations when the exposed workers were subdivided by a cut off at 50 mSv. The frequencies of chromosome breaks in both subgroups of workers were significantly higher than in controls (≤50 mSv, P=0.041; >50 mSv, P=0.018). On the other hand, the frequency of chromatid breaks observed in workers with Hwb >50 mSv was significantly higher than in controls ( P=0.015) or workers with Hwb ≤50 mSv ( P=0.046). Regarding the influence of confounding factors on genetic damage, smoking status and female gender seem to influence the increase in chromosome aberration frequencies in the study population. Overall, these results suggested that chromosome breaks might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation.

Persistence of chromosome aberrations in peripheral lymphocytes from Hodgkin's lymphoma remission patients

Purpose : To analyse spontaneous and in vitro bleomycin-induced chromosome aberrations in peripheral lymphocytes taken from Hodgkin's disease patients after prolonged (up to 31 years) remission periods, and to consider these data from the point of view of the carcinogenic potential of anticancer therapy. Materials and methods : Conventional analysis of chromosome preparations stained with azure-eosin. Results : The mean frequency and patterns of both spontaneous and induced aberrations in remission patients were significantly different from comparison groups (healthy donors and primary Hodgkin's disease patients). Individual values were characterized with high variation and did not show correlation with post-therapy time. New cancer cases diagnosed in remission patients were more frequent in subjects with high chromosome sensitivity to in vitro bleomycin challenge than in patients whose sensitivity to bleomycin was at a control level. Conclusions : The results are interpreted as suggesting that the tumorigenic potential of radiochemotherapy is mediated via induction of genetic instability in exposed cells. Long after the therapy, the instability may become an initiating event in the development of new malignancies in affected tissues, whereas the instability induced in haemopoietic stem cells may reveal itself in peripheral lymphocytes derived from formerly exposed precursors.