Chromosomal aberration frequencies determined by conventional methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic

The rationale for cytogenetic monitoring to determine if safe maximum allowable concentrations (MAC) of genotoxic chemicals are being maintained in a workplace is that exposure levels that do not increase chromosomal aberration frequencies are without harmful effects. Such monitoring, widely used in occupational health programs in the Czech Republic (CR), includes workers exposed to 1,3-butadiene (BD) or other chemicals. Studies of BD exposed workers in the years 1992, 1993, 1994, 1998, and 2004 compared mean frequencies of cells carrying chromosomal aberrations (frequency of aberrant cells=%AB.C.) in exposed workers with those in non-exposed matched controls in the same plant or in other individuals living in the region of the same petrochemical industry. Workers potentially exposed to acrylonitrile at this site were also evaluated in 2000, along with another unexposed matched control group. The %AB.C. values of exposed workers and their controls were also compared with reference values determined for normal individuals (ages 20-59 years) throughout the CR. Substantial discrepancies were noted between subjects in the region of the petrochemical industry (exposed workers and controls) for the years 2000 and 2004 and the reference CR-wide normal values that had been determined during an earlier time period. The matched non-exposed controls at the petrochemical industry site showed a mean %AB.C. value of 1.56+/-1.23% (N=25) in 1998; this rose to a mean of 2.65+/-2.29% (N=33) in 2000. In 2004, values for non-exposed matched controls at the industry site were 2.64+/-1.75% for males (N=25) and 2.38+/-1.74% (N=26) for females. However, the earlier determined CR-wide %AB.C. mean reference values for normal individuals were 1.77+/-1.16% (N=1305) for the interval 1977-1988 and 1.45+/-1.17% (N=2140) for the interval 1991-1999. As both reference values are substantially lower than those determined in 2000 and 2004 for the non-exposed matched controls at the petrochemical industry site, an analysis of the CR-wide mean normal individual reference values for this same 2000-2004 period was conducted. Unexpectedly, it was found that this reference value too had risen to 1.95+/-1.36% (N=1045) and was comparable to the concurrent matched control values at the petrochemical industry site where the monitoring studies were conducted. This substantial increase in %AB.C. values in 2000 and 2004, therefore, has occurred throughout the CR and is probably unrelated to chemicals uniquely present at the petrochemical industry site.     

The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals

Premature (early) centromere division (PCD, i.e., the separation of centromeres during the prometaphase/metaphase of the mitotic cycle) seems to be a possible manifestation of chromosome instability in human chromosome-breakage syndromes. Chromosome instability also frequently occurs in the peripheral blood lymphocytes (PBL) of humans occupationally exposed to clastogenic agents, and is considered an etiologic factor of neoplastic diseases. In order to investigate the importance of PCD in cancer risk assessment, we studied the frequency of PCDs in PBL of 400 Hungarian subjects. The various groups comprised 188 control donors and 212 subjects occupationally exposed to different genotoxic chemicals, such as acrylonitrile (ACN) and/or dimethylformamide (DMF), benzene, cytostatic drugs, ethylene oxide (ETO), mixed exposure in the rubber industry, mixed organic solvents including CCl4, hot oil-mist, bitumen, and polychlorinated biphenyls (PCB). Data were compared with chromosomal aberration frequencies determined in the same samples. PCD yields are significantly higher in populations exposed to mixed chemicals, crude oil and cytostatic drugs, compared with controls. PCDs involving more than three chromosomes are also more frequent in ETO- and oil mist-exposed groups than in the others. The results indicate that the induction of PCDs is neither incidental nor artificial. As a consequence, we suggest that PCD can be developed into a new, exposure-related cytogenetic biomarker for a more adequate occupational cancer risk assessment. A further, follow-up epidemiological and cytogenetic investigation of PCD is in progress.     

Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations

The health concerns have been raised following the enormous increase in the use of wireless mobile telephones throughout the world. This investigation had been taken, with the motive to find out whether mobile phone radiations cause any in vivo effects on the frequency of micronucleated exfoliated cells in the exposed subjects. A total of 109 subjects including 85 regular mobile phone users (exposed) and 24 non-users (controls) had participated in this study. Exfoliated cells were obtained by swabbing the buccal-mucosa from exposed as well as sex-age-matched controls. One thousand exfoliated cells were screened from each individual for nuclear anomalies including micronuclei (MN), karyolysis (KL), karyorrhexis (KH), broken egg (BE) and binucleated (BN) cells. The average daily duration of exposure to mobile phone radiations is 61.26 min with an overall average duration of exposure in term of years is 2.35 years in exposed subjects along with the 9.84+/-0.745 micronucleated cells (MNCs) and 10.72+/-0.889 total micronuclei (TMN) as compared to zero duration of exposure along with average 3.75+/-0.774 MNC and 4.00+/-0.808 TMN in controls. The means are significantly different in case of MNC and TMN at 0.01% level of significance. The mean of KL in controls is 13.17+/-2.750 and in exposed subjects is 13.06+/-1.793. The value of means of KH in exposed subjects (1.84+/-0.432) is slightly higher than in controls (1.42+/-0.737). Mean frequency of broken egg is found to be more in exposed subjects (0.65+/-0.276) as compared to controls (0.50+/-0.217). Frequency of presence of more than one nucleus in a cell (binucleated) is also higher in exposed (2.72+/-0.374) in comparison to controls (0.67+/-0.231). Although there is a slight increase in mean frequency of KH, BE and BN in exposed subjects but the difference is not found statistically significant. Correlation between 0-1, 1-2, 2-3 and 3-4 years of exposure and the frequency of MNC and TMN has been calculated and found to be positively correlated.     

Field-Level Sublethal Effects of Approved Bee Hive Chemicals on Honey Bees (Apis mellifera L)

In a study replicated across two states and two years, we tested the sublethal effects on honey bees of the miticides Apistan (tau fluvalinate) and Check Mite+ (coumaphos) and the wood preservative copper naphthenate applied at label rates in field conditions. A continuous covariate, a colony Varroa mite index, helped us disambiguate the effects of the chemicals on bees while adjusting for a presumed benefit of controlling mites. Mite levels in colonies treated with Apistan or Check Mite+ were not different from levels in non-treated controls. Experimental chemicals significantly decreased 3-day brood survivorship and increased construction of queen supercedure cells compared to non-treated controls. Bees exposed to Check Mite+ as immatures had higher legacy mortality as adults relative to non-treated controls, whereas bees exposed to Apistan had improved legacy mortality relative to non-treated controls. Relative to non-treated controls, Check Mite+ increased adult emergence weight. Although there was a treatment effect on a test of associative learning, it was not possible to statistically separate the treatment means, but bees treated with Apistan performed comparatively well. And finally, there were no detected effects of bee hive chemical on colony bee population, amount of brood, amount of honey, foraging rate, time required for marked released bees to return to their nest, percentage of released bees that return to the nest, and colony Nosema spore loads. To our knowledge, this is the first study to examine sublethal effects of bee hive chemicals applied at label rates under field conditions while disambiguating the results from mite control benefits realized from the chemicals. Given the poor performance of the miticides at reducing mites and their inconsistent effects on the host, these results defend the use of bee health management practices that minimize use of exotic hive chemicals.     

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified.Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age.The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.     

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified.Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age.The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.     

Ethical Issues in the Use of Data from Testing of Human Subjects to Support Risk Assessment

The public understands and supports the ethical use of human subjects in medical research, recognizing the unique role for this type of study in the development of new drugs and therapeutic strategies for treatment of disease. The use of data from human subjects can also be of value in understanding the circumstances under which individuals exposed to chemicals in the food supply, in the workplace, or in the environment might experience toxicity, i.e., in support of risk assessment. However, questions have been raised as to whether this latter type of research is ethical, or can be performed in an ethical manner. Under what circumstances is it acceptable to intentionally expose human subjects to potentially toxic agents? This is an extremely important issue for the risk assessment community to address, because it affects in a fundamental way the types of information that will be available to conduct human health risk assessments. Four papers in this issue offer viewpoints on the value of human data, the circumstances under which human subjects might be exposed to toxic chemicals for research purposes, the ethical problems associated with this research, and the role of human vs. animal data in the development of toxicity values for human health risk assessment     

Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes

A study was conducted to evaluate the genotoxic effect of occupational exposure to formaldehyde on pathology and anatomy laboratory workers. The level of exposure to formaldehyde was determined by use of passive air-monitoring badges clipped near the breathing zone of 59 workers for a total sampling time of 15min or 8h. To estimate DNA damage, a chemiluminescence microplate assay was performed on 57 workers before and after a 1-day exposure. Assessment of chromosomal damage was carried out by use of the cytokinesis-blocked micronucleus assay (CBMN) in peripheral lymphocytes of 59 exposed subjects in comparison with 37 controls matched for gender, age, and smoking habits. The CBMN assay was combined with fluorescent in situ hybridization with a pan-centromeric DNA probe in 18 exposed subjects and 18 control subjects randomized from the initial populations. Mean concentrations of formaldehyde were 2.0 (range <0.1-20.4ppm) and 0.1ppm (range <0.1-0.7ppm) for the sampling times of 15min and 8h, respectively. No increase in DNA damage was detected in lymphocytes after a one-workday exposure. However, the frequency of binucleated micronucleated cells was significantly higher in pathologists/anatomists than in controls (16.9 per thousand+/-9.3 versus 11.1 per thousand+/-6.0, P=0.001). The frequency of centromeric micronuclei was higher in exposed subjects than in controls (17.3 per thousand+/-11.5 versus 10.3 per thousand+/-7.1) but the difference was not significant. The frequency of monocentromeric micronuclei was significantly higher in exposed subjects than in controls (11.0 per thousand+/-6.2 versus 3.1 per thousand+/-2.4, P<0.001), while that of the acentromeric micronuclei was similar in exposed subjects and controls (3.7 per thousand+/-4.2 and 4.1 per thousand+/-2.7, respectively). The enhanced chromosomal damage (particularly chromosome loss) in peripheral lymphocytes of pathologists/anatomists emphasizes the need to develop safety programs.     

Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations

The health concerns have been raised following the enormous increase in the use of wireless mobile telephones throughout the world. This investigation had been taken, with the motive to find out whether mobile phone radiations cause any in vivo effects on the frequency of micronucleated exfoliated cells in the exposed subjects. A total of 109 subjects including 85 regular mobile phone users (exposed) and 24 non-users (controls) had participated in this study. Exfoliated cells were obtained by swabbing the buccal-mucosa from exposed as well as sex–age-matched controls. One thousand exfoliated cells were screened from each individual for nuclear anomalies including micronuclei (MN), karyolysis (KL), karyorrhexis (KH), broken egg (BE) and binucleated (BN) cells. The average daily duration of exposure to mobile phone radiations is 61.26 min with an overall average duration of exposure in term of years is 2.35 years in exposed subjects along with the 9.84 ± 0.745 micronucleated cells (MNCs) and 10.72 ± 0.889 total micronuclei (TMN) as compared to zero duration of exposure along with average 3.75 ± 0.774 MNC and 4.00 ± 0.808 TMN in controls. The means are significantly different in case of MNC and TMN at 0.01% level of significance. The mean of KL in controls is 13.17 ± 2.750 and in exposed subjects is 13.06 ± 1.793. The value of means of KH in exposed subjects (1.84 ± 0.432) is slightly higher than in controls (1.42 ± 0.737). Mean frequency of broken egg is found to be more in exposed subjects (0.65 ± 0.276) as compared to controls (0.50 ± 0.217). Frequency of presence of more than one nucleus in a cell (binucleated) is also higher in exposed (2.72 ± 0.374) in comparison to controls (0.67 ± 0.231). Although there is a slight increase in mean frequency of KH, BE and BN in exposed subjects but the difference is not found statistically significant. Correlation between 0–1, 1–2, 2–3 and 3–4 years of exposure and the frequency of MNC and TMN has been calculated and found to be positively correlated.     

Response of Daphnia to substances released from crowded congeners and conspecifics

The effects of chemicals released from crowded congeners andconspecifics on life history parameters of the freshwater zooplanktersDaphnia cucullata and Daphnia pulex were examined. Length andage at maturity of D. pulex were affected by crowding chemicals.Reproduction was lower in crowded medium, and ephippia wereproduced. Newborn D. pulex in crowded medium were significantlylonger than the controls. The intrinsic rate of population increaseof D. pulex was 14 and 25% lower than the control when exposedto crowded medium from D. cucullata and D. pulex, respectively.Neither urea nor ammonia (at 1 mg l^-1) seemed to be responsiblefor these effects in D. pulex. In D. cucullata, no significanteffect of crowding infochemicals on length and age at maturitywas found. However, crowding chemicals reduced reproduction.No ephippia were produced in crowded medium, but up to 83% non-developingeggs were observed in D. cucullata. Newborns were similarlysized in crowded and standard medium. The intrinsic rate ofpopulation increase of D. cucullata was 44 and 96% lower thanthe control when exposed to crowded medium from D. cucullataand D. pulex, respectively. Clearance rates of D. pulex weresignificantly reduced in crowded media compared with standardmedium, which could partly explain why the animals exposed tocrowding chemicals reacted as if they were food limited.     

Chromosomal aberrations, SCE and urine mutagenicity in workers occupationally exposed to cytostatic drugs

The genetic risk run by workers occupationally exposed to chemicals, including the newly developed cytostatics, was assessed in large chemical laboratories. The exposed group comprising 38 people consisted of chemists, laboratory assistants and pilot plant workers. The average rate of aberrant cells in peripheral blood lymphocytes (AB.C). was 3.9% and the value of break/cell ratio was 0.046. The group of matched controls (N = 18) was found to have 1.5% of AB.C. and 0.020 breaks/cell. In the exposed group, there were, on average, 8.94 SCEs/cell, and in controls, 5.81. Urine mutagenicity tests on Salmonella typhimurium tester strain TA98 revealed a significant increase of activity in 23 (64%) out of 36 urine samples tested as compared to the control group (N = 19) with 4 (21%) positive urine samples. Strain TA100 showed only a weak response to urine mutagens.     

Leather tanning workers: chromosomal aberrations in peripheral lymphocytes and micronuclei in exfoliated cells in urine

A cytogenetic study was performed on workers of a leather tanning industry. Two different approaches for the biological monitoring of the individuals were used: chromosomal aberration analysis in peripheral lymphocytes and the frequency of micronucleated cells exfoliated in urine samples. 26 men working in the sections considered to present a greater risk were included in the study. Controls were 20 men that were not exposed to chemicals. The percentage of abnormal cells was higher in workers than in controls. Smokers showed higher values of chromosome breaks than non-smokers in both groups. These differences were not statistically significant. The percentage of cells with chromatid and chromosome gaps in workers and controls was different (p less than 0.01). A slight but not significant increase in the mean percentage of micronuclei was observed in the exposed group. We conclude that exposure to chemicals during leather tanning did not produce genotoxic effects measured by chromosomal aberrations in peripheral lymphocytes and micronuclei in urine in this group of workers.     

Changes in serum markers indicative of health effects in vineyard workers following exposure to the fungicide mancozeb: an Italian study

The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.     

Karyopathological traits of thyrocytes and exposure to radioiodines in Belarusian children and adolescents following the accident at the Chernobyl nuclear power plant

The Belarus-American (BelAm) thyroid study cohort consists of persons who were 0-18 years of age at the time of exposure to radioactive iodine fallout from the 1986 Chernobyl nuclear power plant accident and who have undergone serial thyroid screenings with referral for fine-needle aspiration biopsy (FNAB) using standardized criteria. We investigated thyrocyte nuclear abnormalities in cytological samples from FNABs in 75 BelAm subjects with single and multiple thyroid nodules and 47 nodular goiter patients from Leningrad, Russia, unexposed to Chernobyl fallout. Nuclear abnormalities examined included internuclear chromosome bridges and derivative nuclei with broken bridges (i.e., "tailed" nuclei), which are formed from dicentric and ring chromosomes and thus may be cellular markers of radiation exposure. Among subjects with single-nodular goiter, thyrocytes with bridges were present in 86.8% of the exposed BelAm cohort compared with 27.0% of unexposed controls. The average frequency of thyrocytes with bridges and with tailed nuclei was also significantly higher in the BelAm subjects than in controls. Among subjects with multinodular goiters, thyrocytes with bridges were present in 75.7% of exposed BelAm patients compared with 16.7% of unexposed controls; thyrocytes with tailed nuclei were observed in all of the BelAm subjects but in only 40% of controls, and the mean frequencies of bridges and tailed nuclei were significantly higher in the exposed group. Unusually, long bridges were detected in 29% of BelAm patients with single-nodular goiters and 35% of those with multinodular goiters, while no such abnormalities were observed among patients from the Leningrad region. In the exposed subjects from BelAm, we also found positive correlations between their estimated dose of Iodine-131 from Chernobyl fallout and the frequency of tailed nuclei (p = 0.008) and bridges (p = 0.09). Further study is needed to confirm that these phenomena represent consequences of radiation exposure in the human organism.     

Serum angiotensin converting enzyme, soluble E-selectin and laminin in subjects occupationally-exposed to volatile organic chemicals and mercury vapour

This study attempts to confirm previous findings of altered serum soluble E-selectin and laminin in workers exposed to volatile organic chemicals VOCs and further explore evidence of endothelial cell disturbances in workers exposed to (VOCs) and mercury vapour. Serum angiotensin converting enzyme (ACE), soluble E-selectin and laminin were measured in a cross sectional study of workers exposed to a small range of VOCs (n = 21), mercury vapour (n = 32) and a control group (n = 50). Both endothelial markers, ACE and E-selectin were significantly higher in mercury- and VOC-exposed workers. Laminin was significantly lower than controls in the VOC exposed. These results confirm our previous initial findings in workers exposed to VOCs of endothelial disturbances and decreased serum levels of a constituent of basement membranes, namely laminin. In the mercury exposed workers who had relatively high occupational exposure for the UK, there was also evidence of endothelial disturbances. The ubiquitous nature of endothelial cells and the underlying structural basement membrane associated with the vasculature means that it is impossible to state with any certainty the site of the action of these chemicals. However due to the ease of absorption of VOCs and mercury via the pulmonary system, and the metabolism of VOCs in the lungs themselves, it is probable that the initial site of the disturbances noted is in lung endothelia and associated basement membrane.     

Influence of PAHs in ambient air on chromosomal aberrations in exposed subjects: international study - EXPAH

The aim of this study was to determine the influence of carcinogenic polycyclic aromatic hydrocarbons (c–PAHs) in complex mixtures in ambient air on DNA damage (chromosomal aberrations) in occupationally exposed subjects measured as percent of aberrant cells (% AB.C.).

There were in total 203 exposed subjects and 150 respective controls in the whole project, allocated in three different European cities – Kosice (Slovakia), Prague (Czech Republic) and Sofia (Bulgaria). The studied population from Kosice (Slovakia) consisted of 106 subjects. From these 51 were exposed policemen and 55 were controls. The Czech population comprised 52 exposed policemen and 50 controls. In Bulgaria, there were two equally numerous exposed groups: 50 policemen and 50 professional bus drivers together with 45 controls. According to personal monitoring, policemen and bus drivers in the Bulgarian capital Sofia were exposed to the highest levels of c-PAHs amongst the exposed subject groups in the cities (45.3 ± 25.9 ng/m³ in policemen resp. 36.1 ± 31.6 ng/m³ in bus drivers in Sofia, 26.8 ± 39.8 ng/m³ for policemen in Kosice and 11.9 ± 11.2 ng/m³ for policemen in Prague), compared to the respective controls (24.9 ± 17.7 ng/m³ for controls in Sofia, 7.9 ± 3.8 ng/m³ for controls in Kosice and 6.2 ± 3.6 ng/m³ for controls in Prague).

We observed the following frequency of % AB.C. scored by conventional method: 2.60 ± 2.64 in exposed policemen and 2.14 ± 1.61 in controls in Kosice (p = n.s.); 2.33 ± 1.53 in exposed policemen and 1.94 ± 1.28 in controls in Prague (p = n.s.); 3.04 ± 1.64 in exposed policemen, respectively, 3.60 ± 1.63 in exposed bus drivers and 1.79 ± 0.77 in the control group in Sofia (p < 0.05, respectively, p < 0.05).

According to data from multiple regression analysis, and group comparison of smokers versus nonsmokers in Sofia also cigarette smoking (p = 0.055) and the age (p = 0.020) seem to play an important role within the aberrant cell formation in addition to the occupational c-PAHs exposure (p = 0.000). Smoking status was the modifying factor for % AB.C. in Kosice (p = 0.020) after multiple regression approach was employed.

In summary, we can say that subjects occupationally exposed to higher levels of c-PAHs in ambient air in Sofia are at greater genotoxic risk compared to those working indoors.     

Retrospective dose estimation in remote period after exposure using different biological methods

Investigation of application of chromosome aberrations of lymphocytes in peripheral blood for biological dosimetry purposes in remote (up to 40 years) period after acute exposure to doses of 1 Gy and more was carried out. The comparative analysis of frequency of unstable and stable (using FISH and G-banding methods) aberrations was performed for 24 subjects accidentally exposed to radiation on nuclear submarines during 1961-1985. Statistically significant increasing of frequency of dicentrics and centric rings was determined in the exposed subjects in remote period after exposure to compare with controls. Their sum frequency in the exposed group varied depending on ARS heaviness from 0.1 to 1.0 aberrations per 100 cells. In control group it was from 0 to 0.2 correspondingly. Translocation frequency (complete + incomplete) fixed by FISH method (2, 4, and 12 chromosomes) varied within the limits of 0.2-16.0 for exposed subjects and 0.3-1.26 translocations per genome per 100 cells for controls. Some examined persons (5 subjects) exposed to accident in 1985 had results of analysis of unstable chromosome aberration in acute period after exposure that allow to estimate obtained doses by dicentrics frequency which having good correlation with ARS heaviness. Individual dosed using traslocation frequency were defined retrospectively in 11 from 21 exposed persons. They correlate with calculated physics doses and doses estimated by haematolotical parameters in acute period and also doses obtained by ESR spectroscopy of tooth enamel in remote period.     

Expression of lymphocyte cell surface markers in workers exposed to different respiratory hazards: biomarkers of occupational respiratory disease

This study was designed to evaluate the potential of flow cytometry to measure biomarkers of airways inflammation in the peripheral blood of two cohorts of workers reporting work related respiratory symptoms, who were exposed to different respiratory hazards. Nine bakers exposed to wheat flour and 10 glass bottle manufacturers exposed to a range of irritant chemicals were selected for study. Phenotypic and inducible cell surface markers were measured by flow cytometry. Results were compared with a control population of 58 volunteers reporting no respiratory problems. The bakers showed a significant increase above control values for cell types associated with inflammation; in particular CD3 CD4 cells p 0.005 and CD4 CD25 cells p 0.01 . In contrast, the workers reporting work related respiratory symptoms who were exposed to a range of irritant chemicals showed a different pattern of cell surface lymphocyte markers, with a significant decrease in the total T cell population p 0.05 . Comparison of results from a subset of smoking controls with the population of bakers who were all heavy smokers confirmed that the increase in CD3 CD4 cells and CD4 CD25 cells could not be ascribed to the effects of smoking alone. We have shown activation of helper T cells in the peripheral blood of bakers reporting work related respiratory symptoms consistent with the changes observed in mild to severe asthmatics. However, workers with similar symptoms who were exposed to irritant chemicals did not show this pattern of phenotypic or inducible cell surface markers, reflecting an absence of airways inflammation in these individuals. Our results suggest that flow cytometry may be of use as an objective test for detecting workers with airways inflammation to allow the identification of workers at risk of developing occupational asthma.     

Expression of lymphocyte cell surface markers in workers exposed to different respiratory hazards: biomarkers of occupational respiratory disease

This study was designed to evaluate the potential of flow cytometry to measure biomarkers of airways inflammation in the peripheral blood of two cohorts of workers reporting work related respiratory symptoms, who were exposed to different respiratory hazards. Nine bakers exposed to wheat flour and 10 glass bottle manufacturers exposed to a range of irritant chemicals were selected for study. Phenotypic and inducible cell surface markers were measured by flow cytometry. Results were compared with a control population of 58 volunteers reporting no respiratory problems. The bakers showed a significant increase above control values for cell types associated with inflammation; in particular CD3 CD4 cells p 0.005 and CD4 CD25 cells p 0.01 . In contrast, the workers reporting work related respiratory symptoms who were exposed to a range of irritant chemicals showed a different pattern of cell surface lymphocyte markers, with a significant decrease in the total T cell population p 0.05 . Comparison of results from a subset of smoking controls with the population of bakers who were all heavy smokers confirmed that the increase in CD3 CD4 cells and CD4 CD25 cells could not be ascribed to the effects of smoking alone. We have shown activation of helper T cells in the peripheral blood of bakers reporting work related respiratory symptoms consistent with the changes observed in mild to severe asthmatics. However, workers with similar symptoms who were exposed to irritant chemicals did not show this pattern of phenotypic or inducible cell surface markers, reflecting an absence of airways inflammation in these individuals. Our results suggest that flow cytometry may be of use as an objective test for detecting workers with airways inflammation to allow the identification of workers at risk of developing occupational asthma.     

Serum angiotensin converting enzyme,soluble E-selectin and laminin in subjects occupationally-exposed to volatile organic chemicals and mercury vapour

This study attempts to confirm previous findings of altered serum soluble E-selectin and laminin in workers exposed to volatile organic chemicals VOCs and further explore evidence of endothelial cell disturbances in workers exposed to (VOCs) and mercury vapour. Serum angiotensin converting enzyme (ACE), soluble E-selectin and laminin were measured in a cross sectional study of workers exposed to a small range of VOCs (n = 21), mercury vapour (n = 32) and a control group (n = 50). Both endothelial markers, ACE and E-selectin were significantly higher in mercury- and VOC-exposed workers. Laminin was significantly lower than controls in the VOC exposed. These results confirm our previous initial findings in workers exposed to VOCs of endothelial disturbances and decreased serum levels of a constituent of basement membranes, namely laminin. In the mercury exposed workers who had relatively high occupational exposure for the UK, there was also evidence of endothelial disturbances. The ubiquitous nature of endothelial cells and the underlying structural basement membrane associated with the vasculature means that it is impossible to state with any certainty the site of the action of these chemicals. However due to the ease of absorption of VOCs and mercury via the pulmonary system, and the metabolism of VOCs in the lungs themselves, it is probable that the initial site of the disturbances noted is in lung endothelia and associated basement membrane.