Anna Biró

Lymphocyte phenotype analysis and chromosome aberration frequency of workers occupationally exposed to styrene, benzene, polycyclic aromatic hydrocarbons or mixed solvents

The aim of our study was to investigate the immunotoxicity of benzene, styrene and polycyclic aromatic hydrocarbon exposure, to establish the correlation between immunological and genotoxicological parameters, and to assess the possible effect of confounding factors such as age and smoking. The immune status of the donors was characterized by measuring the surface antigens of peripheral lymphocytes. The studied antigens were the following: CD3, CD4, CD8, CD14, CD19, CD25, CD38, CD45, CD45RO, CD54, CD56, CD62L, CD71 and HLA-DR. In our studies, we compared the immunological and genotoxicological parameters (chromosome aberration, sister chromatid exchange frequency, unscheduled DNA synthesis) of the different groups with healthy controls. Analysis revealed changes in the expression of surface antigens on peripheral lymphocytes in correlation with exposure. Confounding factors, such as smoking, increased the proportion of CD4 positive T lymphocytes and influenced the surface expression of several antigens. In our investigation the occurrence of chromosome aberrations negatively correlated with CD25 (IL-2R) expression in both CD4 and CD8 positive T cells. The presented data suggest that solvents such as benzene, styrene and PAHs activate peripheral lymphocytes, and cause changes in the incidence of CD25+/CD4+ T lymphocytes that may represent a distinct subset of immune-regulatory T cells.

Formaldehyde-induced chromosomal aberrations and apoptosis in peripheral blood lymphocytes of personnel working in pathology departments

Peripheral blood lymphocytes (PBL) of 37 formaldehyde-exposed women from four pathology departments in Hungary were investigated to collect data on the effects of occupational exposures to formaldehyde and to find a possible relationship between in vivo formaldehyde-induced apoptosis and genotoxic effects. The subjects were divided into two groups: 16 donors exposed to formaldehyde together with various organic solvents, and 21 subjects exposed mainly to formaldehyde. The results were compared with 37 controls (all women) without known occupational exposure. Ambient air concentrations of formaldehyde were measured in three work places, and ranged from 0.23 to 1.21mg/m(3) (mean 0.9mg/m(3)). Measures of genotoxicity included the determination of the frequencies of chromosomal aberrations (CA), sister-chromatid exchange (SCE), HPRT mutations (variant frequency, VF) and the measurement of UV-induced unscheduled DNA-repair synthesis (UDS). The percentages of premature centromere division (PCD) and of cells with a high frequency of SCE (HF/SCE) were also scored. Apoptosis and cell proliferation were determined by flow cytometry. In both formaldehyde-exposed groups, the apoptotic activity and the CA levels in PBLs were significantly higher than in controls. The CA were mostly breaks of the chromatid type. In the second group, which was mainly exposed to formaldehyde, CA were slightly lower in comparison with the group exposed to formaldehyde and solvents, which may be attributed to a different rate of elimination of damaged lymphocytes as a consequence of formaldehyde-induced apoptotic activity. In the second group, a significant decrease of VF and a non-significant increase in HF/SCE were found compared with the control and the other group. In conclusion, the results demonstrate that exposure to formaldehyde induces apoptosis and CA, indicating an excess cancer risk among subjects occupationally exposed to formaldehyde. The results also emphasize the importance of the measurement of occupational air pollutants, such as formaldehyde, in order to avoid genotoxic effects in the workers.

Chemical Safety and Health Conditions among Hungarian Hospital Nurses

Abstract:  In the present study genotoxicological and immunotoxicological follow‐up investigations were made on 811 donors including 94 unexposed controls and 717 nurses with various working conditions from different hospitals (The Hungarian Nurse Study). The nurses were exposed to different chemicals: cytostatic drugs, anesthetic, and sterilizing gases, such as ethylene oxide (ETO) and formaldehyde. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CA], sister chromatid exchange [SCE]), and immune‐toxicological monitoring (ratio of lymphocyte subpopulations, lymphocyte activation markers, and leukocyte oxidative burst). The highest rate of genotoxicologically affected donors (25.4%) was found in the group of cytostatic drug‐exposed nurses. Comparing geno‐ and immunotoxicological effect markers, we found that among genotoxicologically affected donors the frequency of helper T cell (Th) lymphocytes, the ratio of activated T and B cells increased, whereas the oxidative burst of leukocytes decreased. In hospitals with lack of protective measures increased CA yields were observed compared to those with ISO 9001 quality control or equivalent measures. Anemia, serum glucose level, thyroid dysfunctions, benign, and malignant tumors were more frequent in the exposed groups than in controls. The hygienic standard of the working environment is the basic risk factor for the vulnerability of nurses. On the basis of these results, it is suggested, that the used cytogenetic and immunological biomarkers are appropriate to detect early susceptibility to diseases. The Hungarian Nurse Study proved that the use of safety measures could protect against occupational exposure at work sites handling cytostatic drugs, anesthetic, and sterilizing gases.

Immunotoxicity Monitoring of Hospital Staff Occupationally Exposed to Cytostatic Drugs

The aim of our study was to investigate the immunotoxicity of occupational cytostatic drug exposure, and to assess the possible effect of confounding factors, such as age and smoking. In this human study, the immunotoxic effect of antineoplastic drugs was investigated among 306 nurses working in oncology chemotherapy units. Results were compared to 98 non-exposed women. The immune status of the subjects was characterized by immune phenotyping of peripheral blood lymphocytes by flow cytometry, using monoclonal antibodies against surface antigens (CD3, CD4, CD8, CD19, CD25, CD45, CD56 and CD71). The killing ability of neutrophil leukocytes was assessed by the measurement of reactive oxygen intermediate production. Occupational exposure to antineoplastic drugs caused shifts in the major lymphocyte subpopulations, resulting in a statistically significant increase in the ratio of B cells. Cytostatic drug exposure also manifested itself in a decreased frequency of CD25 positive, activated T lymphocytes, and increased oxidative burst of neutrophil granulocytes, both of which may have a functional impact on the immune system of exposed subjects. In the younger subjects exposure also caused a shift in T cell subpopulations: a reduction in the cytotoxic T cell population lead to an elevated Th/Tc ratio. In the exposed group, smoking increased activation of T lymphocyte subpopulations. In conclusion, we have demonstrated that low dose occupational cytostatic drug exposure is immunotoxic, and age and smoking modify the effect of exposure.

Health, Genotoxicology, and Immune Status of Road Pavers in Hungary

Bitumen (asphalts) used for road pavement in Hungary have a low tar content since the 1960s. However, traditional bitumen, as a substance belongs to the IARC Group 2B of carcinogens, because of its tar content, which was radically reduced in the last decades to develop an environmentally friendly substance. Other carcinogens in the working environment which are used, are solvents such as crude oils (Group 1), and diesel exhaust gases (Group 2A). Lifestyle factors also affect the health status of road pavers. The aim of this study was to investigate the changes in health status and geno- and immunotoxicology parameters of asphalt exposed road pavers. Multiple end-point follow-up genotoxicology monitoring was performed in Hungarian road pavers between 1996–1999 and 2003–2006. The latter set was supplemented with immunotoxicological endpoints. Studied subjects were interviewed by a physician to collect data on age, medication, smoking and drinking habits, medical and work histories, and they took part in a routine clinical laboratory check-up, including hematology, liver and kidney function tests and risk factors. The multiple end-point genotoxicology monitor, developed in our laboratory, includes the determination of chromosome aberration (CA), sister-chromatid exchange, and HPRT mutation frequencies and the measurement of DNA repair performed in peripheral blood lymphocytes according to the standard methods. Immunotoxicology monitoring includes determination of lymphocyte subpopulations and the measurement of lymphocyte activation. Altogether 89 asphalt-exposed workers (23 managers, 23 hand pavers, 28 finishers and 15 mixers) were investigated. The results were compared to 33 non-exposed industrial controls. More than half of the studied subjects were active smokers and more than 80% were regular drinkers. Among the exposed the most frequent clinical symptoms were liver and kidney dysfunctions, hypertension, hyperglycemia, high cholesterol, rheumatoid complaints and high count of white blood cells. However, the low exposed management also suffered from hypertension, hyperglycemia and high cholesterol. For genotoxicology monitoring the most significant changes were in the mean CA yields. At the start (1996) CA was increased in exposed subjects. The highest CA was found among mixers, and CA was also elevated among finishers working in closed cabins and pavers cleaning equipment with crude oil. By 1999 the CAs of exposed subjects decreased and remained at the level of industrial controls, except that of mixers still above the control level in 2004. The immunotoxicological tests showed a shift of lymphocyte subpopulations both in the exposed workers and management controls as well as the activation of T and B cells. Alterations found in clinical parameters except rheumatoid complaints can be attributed to the lifestyles of the studied subjects. Data suggest that the main genotoxic agents were exhaust gases in the closed cabins among finishers and crude oil used for cleaning in pavers, as proper ventilation and the use of harmless detergents resulted in the decrease of CA yields.

A nem alkoholos zsírmáj befolyásoló hatása olajipari munkások perifériás lymphocytáinak gén- és immuntoxikológai paramétereire

INTRODUCTION More than half of the Hungarian population is overweight or obese, therefore, non-alcoholic fatty liver is a common problem. According to clinical experience, 20-30% of fatty liver cases is not related to alcohol, but can be linked to diabetes, obesity or metabolic syndrome. AIM The authors studied the correlation between genotoxicity, immuntoxicity and non-alcoholic fatty liver among oil refinery workers. METHOD During this genotoxicological monitoring study the data of 107 exposed were compared to 67 controls. RESULTS 36% of oil refinery workers had non-alcoholic fatty liver, while none of the selected, non-exposed controls had this abnormality. Chromosomal aberrations were elevated from 1.6% to 3.75% in the exposed group, immunotoxicological parameters were also changed, and CD71 positive B-cell ratio increased especially among subjects having non-alcoholic fatty liver. CONCLUSIONS Non-alcoholic fatty liver can negatively influence the genotoxic effects of environmental hazards in workplaces. In the future this condition should be considered during risk assessment. Orv. Hetil., 2016, 157(35), 1394-1402.Absztrakt Bevezetes: A magyarorszagi felnőtt lakossag tobb mint fele tulsulyos vagy elhizott, amelynek hatranyos kovetkezmenye a zsirmaj kialakulasa lehet. Az esetek 20–30%-aban nem alkoholos eredetű, hanem az elhizassal, cukorbajjal vagy metabolikus szindromaval fugghet ossze. Celkitűzes: Jelen dolgozatban az olajipari munkasok koreben fellelhető, nem alkoholos zsirmaj eseteit hasonlitottak ossze a kontrollokkal a gen- es immuntoxikologiai karosodasok fuggvenyeben. Modszer: 107 olajipari munkas adatait hasonlitottak ossze 67 felnőtt ferfi kontrollal. Eredmenyek: Az olajipari dolgozoknal az esetek 36%-aban volt jelen zsirmaj. A kontrollok csoportjaban sem zsirmaj, sem gentoxikologiai elteres nem volt. Az exponaltak koreben a citogenetikai parameterek pozitivitasa a kontrollhoz kepest szignifikansan emelkedett, amit a zsirmaj jelenlete tovabb fokozott. Az immunologiai parameterek kozul a zsirmajban szenvedő exponaltaknal a CD71-pozitiv, vagyis transzferrinreceptort hordozo B-sejtek aranya nőtt. Kovetkeztet...

Genotoxic monitoring of nurses handling cytotoxic drugs

Objective: Several biomarkers may be used to detect harmful exposure and individual susceptibility to cancer. Monitoring of biomarkers related to exposure may have a significant effect on early detection of cell transformation, thereby aiding the primary prevention of various chronic and malignant diseases. Nurses who handle cytotoxic drugs are exposed to carcinogenic agents, which have the potential to interrupt the cell cycle and to induce chromosomal aberrations. The presence of high chromosomal aberrations indicates the need for intervention even when exposure to these carcinogens is low. Methods: Nationally representative samples of 552 nurses were investigated by a follow-up monitoring system. The measured biomarkers were clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CAs] and sister chromatid exchanges [SCEs]) and immunotoxicological monitoring (ratio of lymphocyte subpopulations and lymphocyte activation markers) measured on peripheral blood lymphocytes. Results were compared to the data of 140 healthy, age-matched controls. Results: In nurses exposed to cytostatics, we observed a significantly increased frequency of CAs and SCEs compared with those in the controls. Cytostatic drug exposure also manifested itself in an increased frequency of helper T lymphocytes. Genotoxicological and immunotoxicological changes, as well as negative health effects (i.e., iron deficiency, anemia, and thyroid diseases), increased among cytostatic exposed subjects. Conclusions: These results raised concerns about the protection of nursing staff from chemical carcinogens in the working environment.

Cytogenetic, DNA-repair and Apoptosis Studies in Hospital Nurses’ Peripheral Blood Lymphocytes Occupationally Exposed to Volatile Anesthetic Gases

Background: Health professionals chronically exposed to anesthetic gases in the operating rooms are at higher risk of lung diseases, hematological, immunological and reproductive alterations. Anesthetic gas exposure often exceeds the safety limits, especially in the case of pediatric anesthetists, or when no proper ventilation has been installed in operating theaters. In the present study we assessed the health risk among anesthetics exposed nurses and measured genotoxicological parameters in the presence or absence of confounding factors such as smoking. Methods: The investigations were carried out in 128 subjects exposed to anesthetic gases from health services. The data were compared to 137 healthy, non-exposed controls. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations and sisterchromatid exchange, DNA repair and apoptosis) monitoring system. The exposed group was divided into Halothane and Non-Halothane exposed subgroups to compare the differences within exposures. Results: In the group of health personnel exposed to anesthetic gases, we did not find significant changes in the frequency of chromosome aberrations. Sister-chromatide exchange rates in Halothane exposed and control smokers was increased, compared to nonsmokers. We also found a decrease of apoptosis and inhibition of UV induced DNA repair capacity compared to controls. The exposed individuals had high incidences of malignant diseases (9.3%) mainly breast, skin, and colon cancers. Conclusion: Low level of cytogenetic changes may be related to the decreased apoptotic rate of peripheral blood lymphocytes due to the low risk of misrepair from a decreased DNA-repair capacity. Our results suggest that our biomarkers can be useful in tracking occupational/environmental genotoxic effects among anesthetic gases exposed personnel.

Citosztatikus kezelést végző kórházi dolgozók pajzsmirigy-elváltozásainak géntoxikológiai és immuntoxikológiai vonatkozásai@@@Genetic and immune-toxicologic studies on abnormal thyroid functions in hospital employees exposed to cytostatic drugs

INTRODUCTION Environmental exposure to harmful chemicals may produce severe consequences. AIM The aim of the authors was to perform geno- and immune-toxicological monitoring in female employees occupationally exposed to cytostatic agents in hospitals and compare the findings to those obtained from controls. METHOD Altogether 642 women working in hospital who were occupationally exposed to cytostatic drugs and 262 control women participated in the study. Frequency of chromosome aberrations, immune phenotype and activation of lymphocytes, and the production of reactive oxygen-species in neutrophil granulocytes were determined. RESULTS Markedly higher number (n=39) of thyroid alterations was observed among exposed subjects as compared to controls (n=3). In persons with abnormal thyroid functions, the frequency of chromosome aberrations (3.69%) was significantly higher (3.69%) than in exposed subjects without thyroid alterations (2.43%) and in controls (1.70% and 1.60% in control subjects with and without thyroid alterations, respectively). Significantly increased ratio of helper T lymphocytes and decreased ratio of cytotoxic T cells and transferrin-receptor (CD71) expressing B cells were observed in exposed subjects having abnormal thyroid functions as compared to controls. In addition, the ratio of B cells, CD71 expressing T cells and production of reactive oxygen-intermediates was significantly decreased in exposed subjects with thyroid alterations in comparison to exposed subjects without thyroid alterations. CONCLUSIONS The results indicate increased geno- and immune-toxic effects among exposed subjects having thyroid alterations. Further data are needed to clearly establish the underlying pathophysiological mechanism of this finding.Bevezetes: A veszelyes kornyezeti artalmak komoly kovetkezmenyeket okozhatnak. Celkitűzes: A szerzők citosztatikus kezelest vegző korhazi nőverek (nők) koreben folytattak gen- es immuntoxikologiai vizsgalatokat, es az eredmenyeket kontrollcsoporthoz hasonlitottak. Modszer: A vizsgalatban 642, citosztatikumexponalt korhazi nőver es 262 kontrollszemely (nő) vett reszt. A lymphocytakban meghataroztak a kromoszomaaberraciok gyakorisagat, immunfenotipusat es aktivaltsagat, valamint a neutrophil granulocytakban a reaktivoxigenintermedier-termelest. Eredmenyek: A citosztatikumexponaltak csoportjaban 39, mig a kontrollcsoportban mindossze 3 pajzsmirigybeteggel talalkoztak. Citosztatikumexponalt pajzsmirigybetegeknel szignifikansan gyakoribb volt a kromoszomaaberracio (3,69%), mint a pajzsmirigyelterest nem mutato exponaltaknal (2,43%) es a kontrolloknal (pajzsmirigyelteres nelkuli kontrollszemelyeknel 1,60%, pajzsmirigybetegeknel 1,70%), emellett szignifikansan emelkedett a helper, csokkent a citotoxikus T-lymphocytak es a transzferrinreceptort (CD71) expresszalo B-sejtek aranya a kontrollokhoz kepest. A pajzsmirigyelteressel nem rendelkező citosztatikumexponaltakhoz kepest a citosztatikumexponalt pajzsmirigybetegekben szignifikansan csokkent a B-sejtek es a CD71-et expresszalo T-sejtek aranya, valamint a reaktivoxigenintermedier-termeles. Kovetkeztetesek: Az eredmenyek a pajzsmirigyeltereseket mutato exponaltaknal fokozott gen- es immuntoxikologiai hatasokra utalnak a pajzsmirigyelteresekkel nem rendelkező exponaltakhoz kepest is, amelyek koroki osszefuggeset jovőbeni kutatasok hivatottak eldonteni. Orv. Hetil., 2015, 156(2), 60–66.

Citosztatikus kezelést végzo kórházi dolgozók pajzsmirigy-elváltozásainak géntoxikológiai és immuntoxikológiai vonatkozásai

INTRODUCTION Environmental exposure to harmful chemicals may produce severe consequences. AIM The aim of the authors was to perform geno- and immune-toxicological monitoring in female employees occupationally exposed to cytostatic agents in hospitals and compare the findings to those obtained from controls. METHOD Altogether 642 women working in hospital who were occupationally exposed to cytostatic drugs and 262 control women participated in the study. Frequency of chromosome aberrations, immune phenotype and activation of lymphocytes, and the production of reactive oxygen-species in neutrophil granulocytes were determined. RESULTS Markedly higher number (n=39) of thyroid alterations was observed among exposed subjects as compared to controls (n=3). In persons with abnormal thyroid functions, the frequency of chromosome aberrations (3.69%) was significantly higher (3.69%) than in exposed subjects without thyroid alterations (2.43%) and in controls (1.70% and 1.60% in control subjects with and without thyroid alterations, respectively). Significantly increased ratio of helper T lymphocytes and decreased ratio of cytotoxic T cells and transferrin-receptor (CD71) expressing B cells were observed in exposed subjects having abnormal thyroid functions as compared to controls. In addition, the ratio of B cells, CD71 expressing T cells and production of reactive oxygen-intermediates was significantly decreased in exposed subjects with thyroid alterations in comparison to exposed subjects without thyroid alterations. CONCLUSIONS The results indicate increased geno- and immune-toxic effects among exposed subjects having thyroid alterations. Further data are needed to clearly establish the underlying pathophysiological mechanism of this finding.Bevezetes: A veszelyes kornyezeti artalmak komoly kovetkezmenyeket okozhatnak. Celkitűzes: A szerzők citosztatikus kezelest vegző korhazi nőverek (nők) koreben folytattak gen- es immuntoxikologiai vizsgalatokat, es az eredmenyeket kontrollcsoporthoz hasonlitottak. Modszer: A vizsgalatban 642, citosztatikumexponalt korhazi nőver es 262 kontrollszemely (nő) vett reszt. A lymphocytakban meghataroztak a kromoszomaaberraciok gyakorisagat, immunfenotipusat es aktivaltsagat, valamint a neutrophil granulocytakban a reaktivoxigenintermedier-termelest. Eredmenyek: A citosztatikumexponaltak csoportjaban 39, mig a kontrollcsoportban mindossze 3 pajzsmirigybeteggel talalkoztak. Citosztatikumexponalt pajzsmirigybetegeknel szignifikansan gyakoribb volt a kromoszomaaberracio (3,69%), mint a pajzsmirigyelterest nem mutato exponaltaknal (2,43%) es a kontrolloknal (pajzsmirigyelteres nelkuli kontrollszemelyeknel 1,60%, pajzsmirigybetegeknel 1,70%), emellett szignifikansan emelkedett a helper, csokkent a citotoxikus T-lymphocytak es a transzferrinreceptort (CD71) expresszalo B-sejtek aranya a kontrollokhoz kepest. A pajzsmirigyelteressel nem rendelkező citosztatikumexponaltakhoz kepest a citosztatikumexponalt pajzsmirigybetegekben szignifikansan csokkent a B-sejtek es a CD71-et expresszalo T-sejtek aranya, valamint a reaktivoxigenintermedier-termeles. Kovetkeztetesek: Az eredmenyek a pajzsmirigyeltereseket mutato exponaltaknal fokozott gen- es immuntoxikologiai hatasokra utalnak a pajzsmirigyelteresekkel nem rendelkező exponaltakhoz kepest is, amelyek koroki osszefuggeset jovőbeni kutatasok hivatottak eldonteni. Orv. Hetil., 2015, 156(2), 60–66.