Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer's disease, Parkinson's disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood-brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population.

[Concise history of toxicology - from empiric knowledge to science]. / A toxikológia rövid története ­ a tapasztalattól a tudományig.

Toxicology is a science of poisonings by xenobiotics and endogenous physiological changes. Its empiric roots may be traced back to the emerging of the human race because the most important pledge of our predecessors' survival was the differentiation between eatable and poisonous plants and animals. In the course of social evolution, there were three main fields of using poisons: 1) hunting and warfare, 2) to settle social tensions by avoiding military conflicts through hiding strategy of eliminating enemies by toxic substances, 3) medicines applied first as anti-poisons and later by introducing strong substances to defeat diseases, but paradoxically active euthanasia is also a part of the whole story. The industrial revolution of the 19th century changed the sporadic occupational diseases to mass conditions. Later the chemical industry and subsequently the mass production of synthetic materials turned out as a global environmental catastrophe. This latest change initiated the emerging of ecological toxicology which is a future history of the concerning ancient science. Orv Hetil. 2018; 159(3): 83-90.

[Influence of non-alcoholic fatty liver disease on geno- and immunotoxic alterations of peripheric blood lymphocytes of oil refinery workers]. / 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.

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.

[Genetic and immune-toxicologic studies on abnormal thyroid functions in hospital employees exposed to cytostatic drugs]. / 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.

[Use of comet assay for the risk assessment of oil- and chemical-industry workers]. / Comet assay alkalmazása olaj- és vegyipari exponált dolgozók kockázatbecslésében.

INTRODUCTION: The comet assay is a fluorescent microscopic method that is able to detect DNA strand-breaks even in non-proliferative cells in samples with low cell counts. AIM: The aim of the authors was to measure genotoxic DNA damage and assess oxidative DNA damage caused by occupational exposure in groups exposed to benzene, polycyclic aromatic carbohydrates and styrene at the workplace in order to clarify whether the comet assay can be used as an effect marker tool in genotoxicology monitoring. METHOD: In addition to the basic steps of the comet assay, one sample was treated with formamido-pirimidine-DNA-glycolase restriction-enzyme that measures oxidative DNA damage. RESULTS: An increase was observed in tail moments in each group of untreated and Fpg-treated samples compared to the control. CONCLUSIONS: It can be concluded that occupational exposure can be detected with the method. The comet assay may prove to be an excellent effect marker and a supplementary technique for monitoring the presence or absence of genotoxic effects.

[The effect of Kaqun-water on the immune parameters of healthy volunteers]. / A Kaqun víz hatása egészséges önkéntesek immunológiai paramétereire.

INTRODUCTION: Kaqun-water contains a high amount of stable oxygen, which absorbed through the skin and intestinal tract, increases tissue oxygenation. AIM: The aim of the authors was to evaluate the effect of 21 days of Kaqun-water treatment on the immune parameters of healthy volunteers. METHOD: Subpopulations of lymphocytes were determined by immune phenotyping, and CD25 and CD71 activation antigens were used to assess lymphocyte activation. Production of reactive oxygen intermediates was measured to determine the killing capacity of neutrophil granulocytes. Data was analysed with repeated measures ANOVA. RESULTS: The reactive oxygen intermediate production of neutrophils increased significantly in stimulated samples during three weeks of Kaqun-water treatment. The percent of activated, CD25 positive T and helper T cells, and the ratio of NK cells increased. CONCLUSIONS: The increase in oxygen concentration caused by Kaqun-water treatment affects several immune functions: the killing potential of neurophil granulocytes is enhanced, the activation of lymphocytes shows an increased activity of immune function, and the elevated ratio of NK cells may help combat virally infected and tumorous cells.

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.

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.

[Theory and practice of primary cancer prevention]. / A rák elsôdleges megelôzésének elmélete és gyakorlata. Krompecher emlékelôadás, 2006.

The primary aim of cancer prevention is to stop carcinogens from entering the body. Since the low doses involved in carcinogenesis do not cause true toxicological effects, usual toxicological analytic methods do not allow the detection of the early effects of carcinogens. Exposure to chemical carcinogens causes damage to nuclear chromatin, the most vulnerable part of the cell, by inducing DNA damage, chromosomal abnormalities and mutations, which foreshadow the danger of cancer development. In such cases intervention is possible in two ways. On the one hand, we attempt to remove the causative agent from the environment, while on the other we aid the elimination of somatic mutations. The latter is called active prevention; the introduction of substances into the body that can help the elimination of defective cells (apoptosis induction) or stop processes responsible for elongation errors (i.e. with antioxidants). Concerning our own studies, we present the results of 25 years of research on the genotoxicological characteristics of workers exposed to various chemicals, which show that active prevention can in fact be effective in conjunction with information on specific biomarkers. We present in detail the genotoxic changes found in hospital nurses who routinely administer intravenous cytostatic therapy, and the relationship of these changes to their immunotoxic and clinical laboratory parameters. Genotoxic substances decrease the oxidative burst and natural killer (NK) cell activity, which may explain the immunosuppressive effects of occupational exposures. We also present the detailed results of a follow-up study involving two groups of industrial workers. We monitored the status of workers involved in benzene production for 15 years and of asphalt industry workers for 8 years. In both studies we concluded that genotoxic effects can be decreased by ensuring appropriate working conditions, while a temporary lapse in these conditions or accidental changes lead to increases in genotoxic parameters. Since genotoxic effects develop over an extended period (4-5 months), they are independent of hygienic conditions at any single inspection and, thus, their detection also offers a way to ascertain true exposure levels. Our studies also show a connection between genotoxic effects and immune function, which is adversely affected not only by occupational exposures, but also by medications and smoking. From our results with workers in the oil and asphalt industries, we concluded that the levels of chromosomal aberrations (CAs) and sister chromatid exchange (SCE) increase in proportion to exposure levels and decrease with a certain delay following the attenuation of the exposure. We could not detect an increased frequency of any chronic disease in industrial workers. The increased numbers of iron deficiency anemia and thyroid disease in nurses providing cytostatic therapy was, however, related to their occupational exposure.

Chemical safety and health conditions among Hungarian hospital nurses.

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.

[The state of health of oncology nurses characterized by genetic and immunotoxicologic biomarkers]. / Citosztatikumokkal exponált nôvérek egészségi állapotának jellemzése gén- és immuntoxikológiai módszerekkel.

Statistical data indicate a chronic shortage of work-force due to overwork, ill health state and increased risk of chronic noninfectious diseases in Hungarian health care personnel, which needs investigations in order to decrease the risk. Nurses of oncology units, often exposed to carcinogens when preparing and handling cytostatic drugs, are especially at high risk. In the present publication we report a complex clinical, geno- and immunotoxicology risk assessment of altogether 500 nurses, performed during the last 10 years at various oncology units in Hungary. The obtained results indicate that the health status of nurses at oncology units is better than the Hungarian average, especially of hypertonia and type II diabetes. However, the prevalence of iron deficiency anemia and different thyroid gland diseases is significantly higher than those of the controls matched for sex and age. The results suggest that iron deficiency can potentiate the resistance to insulin, i.e. the persistence of iron deficiency may increase the serum glucose levels and thus the risk of diabetes. Among the studied geno- and immunotoxicology biomarkers, the frequency of chromosome aberrations, sister chromatid exchange and B lymphocytes was significantly increased compared to the matched controls. The obtained alterations demonstrate the occupational exposure of the nurses to cytostatic drugs, thus the introduction of more strict hygienic controls and compliance with the European Union chemical safety regulations is necessary.

[The use of biomarkers in cancer prevention]. / Biomarkerek alkalmazása a rákprevencióban.

Biomarkers in cancer prevention are increasingly important tools in primary prevention and in intervention by chemopreventive agents. Biomarkers can be utilized as indicators of exposures, effects and individual susceptibility to cancer. Sampling of biomarkers in relation to exposure may have a great impact on the reliability of mechanism of action. The recent developments in genomics provides us with an opportunity to investigate simultaneously numerous oncogenes, tumor-suppressor genes, phenotypic changes in proteins and to utilize the same samples for better understanding of possible ways to disrupt carcinogenesis. Identification of high cancer risk biomarkers is possible also by traditional molecular genetics techniques. Chromosomal studies are based on peripheral blood lymphocyte (PBL) cultures, which may present mutation as a cytogenetic change on chromosome structures. International databases are available for evaluation of high cancer risk among those people who are carrying high incidence of chromosomal aberrations. The biomarkers are suitable to indicate the need for intervention in high risk groups. In those cases, where removal of environmental hazards are not efficient enough in preventive measures since genetic damages are irreversible, it may be possible to introduce chemoprevention at the same time, which includes changes in lifestyle, smoking and drinking habits as well as prescription of vitamins, antioxidants, minerals etc. This paper summarizes the current knowledge on biomarkers indicative of high risk groups and/or individual susceptibility measured by different methodologies, mainly based on Hungarian human genotoxic monitoring studies, which may help to understand the use of biomarkers in everyday medical practice.

Risk management among benzene-exposed oil refinery workers.

Ten benzene-exposed oil refinery workers were genotoxicologically monitored in an annual follow-up study between 1990 and 2003 and compared with 87 industrial and 26 matched controls. Each of the exposed subjects suffered from several intercurrent non-infectious diseases such as joint, rheumatic, gastric and dental problems, as well as kidney and liver dysfunctions. The structural chromosome aberration (CA) yields of the exposed donors suggested a dose-dependent response to the mean peak benzene concentrations in the ambient air. Sister chromatid exchange (SCE), high-frequency SCE, DNA repair, and cell proliferation data also indicated the presence of genotoxic exposure at the workplace. The results of the biological and genotoxicological monitoring indicated the need of intervention (primary prevention of occupational exposure-related chronic non-infectious diseases) including the introduction of zero tolerance of benzene emission, health control, and education with motivation to change life-styles. The decrease in CA frequencies considered as the most established genotoxicological effect markers indicated the positive changes due to the achieved zero tolerance at the workplaces. The results also demonstrated the effectiveness of a trilateral co-operation between the health services, the employer and the employee in order to reduce the risk of the exposure-related intercurrent non-infectious diseases and to prevent further deterioration of the health state of the workers.

Chemopreventive properties of trans-resveratrol against the cytotoxicity of chloroacetanilide herbicides in vitro.

The beneficial effect of trans-resveratrol (RESV) on health is well documented. Our aim was to study the putative preventive effect of RESV on the cytotoxicity of frequently used herbicides (alachlor, acetochlor). Estrogen receptor positive (ER+) MCF-7 human mammary carcinoma, HepG2 (ER+) human hepatocellular carcinoma and VERO estrogen receptor negative (ER-) non-transformed monkey fibroblast cell lines were treated with alachlor and acetochlor (2-500 microg/ml) as toxic agents, and RESV (10 microM) as preventive agent. The MTT dye reduction assay was performed to test cytotoxicity, and flow cytometry to test cell proliferation and apoptosis. RESV is not cytotoxic in the concentration range of 1-100 microM on neither cell lines examined after 24 h, but cytotoxic on Vero and MCF-7 cells at 100 microM after 48h, and on all three cell lines after 72 h. On both ER+ cell lines a stimulation of viability occurs in the low concentration range (0.5-12.5 microM) as detected by the MTT assay. Cell cycle analysis of the culture shows a significant increase of S-phase cells at low concentrations of RESV (10-50 microM) and a decrease in the 100-200 microM concentration range. The ratio of apoptotic cells significantly increases after the administration of 50 microM RESV, depending on the incubation time. The cytotoxicity of 20-65 microg/ml alachlor and 10-65 microg/ml acetochlor was significantly decreased by the addition of 10 microM RESV in Vero ER- cells whereas no significant change was detected on ER+ cell lines MCF-7 and HepG2. These results show that RESV protects non-transformed ER- cells, but has no such effect on ER+ tumor cells.

[Predictive value of human genotoxicological biomarkers in the primary prevention of chronic non-infectious diseases]. / A humán géntoxikológiai biomarkerek prediktivitása a betegségek megelôzésében.

The main goal of biomarker research in the frame of primary prevention of chronic diseases is the prevention of appearance of clinical symptoms by an early recognition of the process leading to the symptoms. By the use of well-established biomarkers one can detect such tendencies finally leading to the manifestation of the disease far before the progress turns irreversible. As several parameters play role in such processes, the estimation of biological changes with the help of biomarkers is a precise and relatively simple means of the prevention. Indications of intervention in order to prevent the manifestation of a disease are rather determined by the nature but not the number of alterations. The use of genetic screening and monitoring by adequate biomarkers provide us with a new opportunity to measure such qualitative changes rather than the quantitative ones, ensuring a great improvement to the previous methods. The use of qualitative parameters as a routine method instead of the classic quantitative measures might represent a challenge for current prevention policies in Europe to approach health problems and safety at work. When the biomarkers give positive results that means a high probability to be at risk but not yet the manifestation of a certain illness. This stage may be relevant to the early onset of certain pathological processes, but it does not necessarily turn to a performed disease. In consequence a so-called positive result might cause unnecessary disturbances for the probands leading to ethical issues of risk communication. The monitoring system, however, should find acceptable communication strategies for the high-risk conditions detected by the well-established biomarkers.

[Biomarker indicators of chemoprevention among subjects occupationally exposed to metals]. / A kemoprevenció biomarker indikátorai fémexponáltak körében.

Chemoprevention with chelating agent Humetta for three months was performed, due to anaemia and other haematologic disorders, immunotoxicological alterations and/or increased chromosome aberration rate among galvanisers and goldsmiths occupationally exposed to precious and heavy metals. Twenty-two of altogether 47 subjects took part voluntarily in the chemoprevention, and the rest of the subjects served as untreated controls. Complex clinical laboratory testing including detailed anamneses; genotoxicological and immunotoxicological monitoring were performed before and after administration of chemopreventive agent. After chemoprevention a significant improvement was observed in anaemia and serum glucose levels, while a less marked improvement was found in serum cholesterol levels and liver functions. Altered chromosome aberration and apoptotic cell fraction also tended to normalise after treatment. Immunological parameters were not affected by the treatment. The obtained results may suggest that chemoprevention with chelating agents as Humetta can help in the prevention of harmful effects of occupational exposures to metals.

[Characterization of chemically exposed groups by immunotoxicological methods]. / Immuntoxikológiai vizsgálatok alkalmazása a kockázati csoportok jellemzésében.

At the National Institute of Chemical Safety we have surveyed the immunological status of donors from the oil industry, health services, and metallurgy exposed to different immunotoxic compounds. Their data were compared to those of healthy, non-exposed controls. Our aim was to study the relationship between immunotoxic exposure and immune function, and to establish a system of immunological parameters by which chemical exposure can be specifically monitored. Subpopulations and activation of lymphocytes was measured by flow cytometry, using immunophenotyping of peripheral blood lymphocytes. In the groups exposed to immunotoxic compounds we found an increase in helper, and a decrease in cytotoxic T lymphocytes, leading to a shift in Th/Tc ratios. These phenomena are not substance specific, but relate to chemical exposure. The lymphocytes of exposed groups showed a higher proportion of activated cells, but there was a difference in the expressed activation markers. Our results suggest that characterizing lymphocyte subpopulations and activation markers on PBL of donors is a useful tool in tracking environmental immunotoxic effects.

Effect of simultaneous administration of Avemar and cytostatic drugs on viability of cell cultures, growth of experimental tumors, and survival tumor-bearing mice.

Avemar (Biromedicina Co., Budapest, Hungary), a wheat germ preparation with immunomodulant and antimetastatic activity, was applied simultaneously with cytostatic drugs of different modes of action, in vitro and in vivo, in order to find out whether this simultaneous administration exerts an antagonistic or a synergistic effect on the viability of cell cultures, tumor growth, and survival of animals, inoculated with a transplantable mouse tumor (3LL-HH). In vitro, Avemar did not influence the effect on the viability of MCF-7, HepG2, or Vero cells, exerted by Dacarbazine, 5-fluorouracyl, or Adriblastina. In vivo, Avemar, combined with Endoxan, Navelbine, and doxorubicin, did not prevent the tumor growth inhibitory effect of the cytostatic drugs. The combination of Avemar with the cytostatic drugs did not increase the toxicity of the cytostatic compounds, and did not exert any toxic effect. Avemar may be administered together with cytostatic drugs, without the risk of increasing toxicity or decreasing antiproliferative activity.