8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene.

The present study aims to investigate the relation between exposure to low-dose benzene and the occurrence of oxidative DNA damage in gasoline station workers, as well as the possible role of interfering or confounding factors. Urine levels of 8-OHdG were evaluated by a competitive immunoassay in a group of 80 men, employed in gasoline stations located in East Sicily and compared with a control group (n = 63) of male office employees not occupationally exposed to benzene. Information regarding socio-demographic characteristics, lifestyle and job-related records were provided through a questionnaire. Significantly higher (p < 0.05) urinary t,t,-MA and 8-OHdG levels were observed in gasoline station attendants compared to subjects not exposed to benzene. Pearson's test demonstrated a strong correlation (r = 0.377, p < 0.001) between 8-OHdG and benzene exposure level. 8-OHdG significantly correlated also with job seniority, (r = 0.312, p < 0.01), whereas the relation with age resulted weaker (r = 0.242, p < 0.05). Multiple linear regression analysis, performed to exclude a role for confounding factors, showed that variables like gender, smoking habit, alcohol consumption and BMI did not have a significant influence on the measured biomarkers. No subject enrolled in the study presented signs or symptoms of work-related disease or other illness linked to oxidative stress. These results suggest that low-level chronic exposure to benzene among gasoline station attendants can determine oxidative damage on DNA, as indicated by alteration of 8-OHdG which may represent a non-invasive biomarker of early genotoxic damage in exposed subjects.

Immunological effects of occupational exposure to lead (Review).

It is well-known that occupational and environmental exposure to several factors, including benzene, heavy metals, chemicals and mineral fibers, is associated with the risk of developing a great number of diseases. Numerous studies have been carried out in order to investigate the mechanisms of toxicity of these substances, with particular regard to the possible toxic effects on the immune system. However, little is known about the influence of heavy metals, such as lead, on the immune system in human populations. Lead is a heavy metal still used in many industrial activities. Human exposure to lead can induce various biological effects depending upon the level and duration of exposure, such as toxic effects on haematological, cardiovascular, nervous and reproductive systems. Several studies demonstrated that exposure to lead is associated to toxic effects also on the immune system, thus increasing the incidence of allergy, infectious disease, autoimmunity or cancer. However, the effects of lead exposure on the human immune system are not conclusive, mostly in occupationally exposed subjects; nevertheless some immunotoxic abnormalities induced by lead have been suggested. In particular, in vivo, in vitro and ex vivo lead is able to improve T helper 2 (Th2) cell development affecting Th1 cell proliferation. Further studies are required to better understand the mechanisms of lead immunotoxicity and the ability of lead to affect preferentially one type of immune response.

Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans (Review).

It is well known that pesticides are widely used compounds. In fact, their use in agriculture, forestry, fishery and the food industry has granted a huge improvement in terms of productive efficiency. However, a great number of epidemiological surveys have demonstrated that these toxic compounds can interact and exert negative effects not only with their targets (pests, herbs and fungi), but also with the rest of the environment, including humans. This is particularly relevant in the case of workers involved in the production, transportation, preparation and application of these toxicants. Accordingly, a growing body of evidence has demonstrated the correlation between occupational exposure to pesticides and the development of a wide spectrum of pathologies, ranging from eczema to neurological diseases and cancer. Pesticide exposure is often quite difficult to establish, as many currently used modules do not take into account all of the many variables that can occur in a diverse environment, such as the agricultural sector, and the assessment of the real risk for every single worker is problematic. Indeed, the use of personal protection equipment is necessary while handling these toxic compounds, but education of workers can be even more important: personal contamination with pesticides may occur even in apparently harmless situations. This review summarises the most recent findings describing the association between pesticide occupational exposure and the development of chronic diseases.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well­designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Benzene exposure is associated with epigenetic changes (Review).

Benzene is a volatile aromatic hydrocarbon solvent and is known as one of the predominant air pollutants in the environment. Chronic exposure to benzene is known to cause aplastic anemia and increased risk of acute myelogenous leukemia in humans. Although the mechanisms by which benzene causes toxicity remain to be fully elucidated, it is widely accepted that its metabolism is crucial to its toxicity, with involvement of one or more reactive metabolites. Novel approaches aimed at evaluating different mechanisms by which benzene can impact on human health by altering gene regulation have been developed. Among these novel approaches, epigenetics appears to be promising. The present review article summarizes the most important findings, reported from the literature, on epigenetic modifications correlated to benzene exposure. A computerized search in PubMed was performed in November 2014, using search terms, including 'benzene', 'epigenetic', 'histone modifications', 'DNA methylation' and 'microRNA'. Epidemiological and experimental studies have demonstrated the potential epigenetic effects of benzene exposure. Several of the epigenomic changes observed in response to environmental exposures may be mechanistically associated with susceptibility to diseases. However, further elucidation of the mechanisms by which benzene alters gene expression may improve prediction of the toxic potential of novel compounds introduced into the environment, and allow for more targeted and appropriate disease prevention strategies.

Molecular biomarkers of oxidative stress and role of dietary factors in gasoline station attendants.

Exposure to benzene promotes oxidative stress through the production of ROS, which can damage biological structures with the formation of new metabolites which can be used as markers of oxidant/antioxidant imbalance. This study aims to assess modifications in circulating levels of advanced oxidation protein products (AOPP), advanced glycation end-products (AGE) and serum reactive oxygen metabolites (ROMs) in a group of gasoline station attendants exposed to low-dose benzene and to evaluate the influence of antioxidant food intake on these biomarkers of oxidative stress. The diet adopted by the population examined consisted of compounds belonging to the classes of terpenoids, stilbenes and flavonoids, notably resveratrol, lycopene and apigenin. Ninety one gasoline station attendants occupationally exposed to benzene and 63 unexposed male office workers were recruited for this study. Urinary trans, trans-muconic acid (t,t-MA) concentration, determined to assess individual exposure level, resulted significantly higher in exposed workers. In subjects exposed to benzene, we observed a significant increase (p < 0.001) in ROMs and AOPP levels, which were also negatively correlated with fruit and vegetables consumption. By contrast, AGE did not show a significant increase and consequently any relation with antioxidant food intake. Only ROMs, representing a global biomarker of oxidative status, resulted correlated to t,t-MA levels (p < 0.01), probably due to low-dose exposure. Increase of ROS induced by reactive benzene metabolites may promote specific biochemical pathways with a major production of AOPP, which seem to represent a more sensitive biochemical marker of oxidative stress in workers exposed to benzene compared to AGE. Furthermore, this is the first study demonstrating ROMs increment in subject exposed to benzene. These biomarkers may be useful for screening purposes in gasoline station workers and other subjects exposed to low-dose benzene. Moreover, a diet rich in fruits and vegetables demonstrated an inverse association with the levels of oxidative stress markers, suggesting a protective role of antioxidant food intake in workers exposed to oxidant agents.

Low-dose occupational exposure to benzene and signal transduction pathways involved in the regulation of cellular response to oxidative stress.

AIMS: Benzene metabolism seems to modulate NF-κB, p38-MAPK (mitogen-activated protein kinase) and signal transducer and activator of transcription 3 (STAT3) signalling pathways via the production of reactive oxygen species. This study aims to evaluate the effects of low-dose, long-term exposure on NF-κB, STAT3, p38-MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) signal transduction pathways in peripheral blood mononuclear cells in gasoline station attendants. The influence of consumption of vegetables and fruits on these pathways has also been evaluated. MAIN METHODS: A total of 91 men, employed in gasoline stations located in eastern Sicily, were enrolled for this study and compared with a control group of 63 male office workers with no history of exposure to benzene. The exposure was assessed by measuring urinary trans,trans-muconic acid (t,t-MA) concentration. Quantitative analyses were performed for proteins NF-κB p65, phospho-NF-κB p65, phospho-IκB-α, phospho-SAPK/JNK, phospho-p38 MAPK and phospho-STAT3 using an immunoenzymatic assay. KEY FINDINGS: The results of this study indicate significantly higher t,t-MA levels in gasoline station attendants. With regard to NF-κB, phospho-IκB-α and phospho-STAT3 proteins, statistically significant differences were observed in workers exposed to benzene. However, no differences were observed in SAPK/JNK and p38-MAPK activation. These changes were positively correlated with t,t-MA levels, but only phospho-NF-κB p65 was associated with the intake of food rich in antioxidant active principles. SIGNIFICANCE: Chronic exposure to low-dose benzene can modulate signal transduction pathways activated by oxidative stress and involved in cell proliferation and apoptosis. This could represent a possible mechanism of carcinogenic action of chronic benzene exposure.

Oxidative stress biomarkers and paraoxonase 1 polymorphism frequency in farmers occupationally exposed to pesticides.

Previous evidence has demonstrated that chemical classes of pesticides, including organophosphates (OP), can induce oxidative stress in exposed workers. The resulting increase in free radicals causes damage to biological macromolecules, and promotes the formation of novel compounds, including advanced glycation end products (AGE) and advanced oxidation protein products (AOPP). The present study aimed to evaluate the common genetic polymorphisms of the paraoxonase 1 (PON1) gene in a group of 55 farmers exposed to pesticides, as well as the association between these polymorphisms and serum levels of AGE and AOPP. The 192Q wild­type (WT) allele was present at a significantly higher frequency, compared with the 192R mutated allele (0.74 and 0.26, respectively). The WT allele was predominantly represented by the homozygote 192QQ genotype (51%). The mutated 192QR heterozygotic allele was prevalent, at a frequency of 45.4%, whereas the mutated homozygotes were present at a frequency of 3.6%. A significant decrease in the levels of AGE and AOPP was observed in farmers exhibiting the homozygotic 192RR mutated genotype (14,7221 AU/ml and 0.64 nmol/ml, respectively), compared with the WT genotype (16,1400 AU/ml and 1.76 nmol/ml, respectively), and 192QR genotype (15,2312 AU/ml and 1.60 nmol/ml, respectively). Therefore, due to the high catalytic activity of PON1, the 192RR genotype provides an important genetic predictor of the toxic effects associated with OP pesticide exposure. It determines a minor risk of developing oxidative damage following pesticide exposure, and measuring the levels of AOPP may provide a novel biomarker for oxidative damage in subjects exposed to OP.

Seroprevalence and occupational risk survey for Coxiella burnetii among exposed workers in Sicily, Southern Italy.

OBJECTIVES: The aim of this survey was to assess the seroprevalence of antibodies against Coxiella burnetii (C. burnetii) in subjects at risk of exposure in Sicily, Southern Italy. MATERIAL AND METHODS: Prevalence of IgG antibodies to C. burnetii phase II antigens was evaluated by ELISA in a group of 140 workers at risk of exposure (38 veterinarians, 38 slaughterhouse workers, 44 livestock handlers, 20 laboratory and technical personnel) included in a medical surveillance program and in 42 control subjects. Positive samples were classified as suggestive of prior exposure to C. burnetii. RESULTS: Antibodies against C. burnetii were detected in 88 out of 140 (62.9%) exposed workers and in 6 out of 42 (14.3%) subjects of the control group. The variables evaluated did not seem to have a significant effect on seropositivity to Coxiella with the exception of symptoms in the last 6 months preceding the survey. CONCLUSIONS: Our study demonstrated a high seroprevalence of C. burnetii in the group of exposed workers in comparison to non-exposed subjects of the control group. Clinical illness appears to be rare; nevertheless, physicians should consider Q fever in patients with compatible symptoms and occupational exposure to animals and their products. As aerosols represent the main route of infection in animals and humans, these workers are strongly advised to wear respiratory masks. In addition, occupational physicians should consider routine serologic evaluation and vaccination of occupationally exposed workers.

Occupational exposure to anaesthetic gases and high-frequency audiometry.

OBJECTIVES: Occupational exposure to anaestethic gases has been suggested to induce auditory damages. The aim of this study is to investigate high-frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system. METHODS: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care. We have used tonal audiometry as well as high-frequency one. We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases. Results were compared statistically. RESULTS: Results show a strong correlation (p = 0.000) between left and right ear responses to all the audiometric tests. The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies (2000 HZ p = 0.009 and 4000 Hz p = 0.04); in high-frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way (10,000 Hz p = 0.025, 12,000 Hz p = 0.008, 14,000 Hz p = 0.026, 16,000 Hz p = 0.08). The highest values are the ones related to exposed subjects both in standard (2000 Hz p = 0.01, 4000 Hz p = 0.02) and in high-frequency audiometry (10,000 Hz p = 0.011, 12,000 Hz p = 0.004, 14,000 Hz p = 0.012, 16,000 Hz p = 0.004). CONCLUSION: Results, even if preliminary and referred to a low-range sample, show an involvement of the anatomic structure responsible for the perception of high-frequency audiometric responses in subjects exposed to anaesthetic gases.

IL-17 and IL-22 serum levels in greenhouse workers exposed to pesticides.

INTRODUCTION: Altered immune function may be an indicator of increased potential for the development of immunologically based diseases such as cancer, hypersensitivity and autoimmunity. MATERIALS AND METHODS: To investigate whether Th17 and Th22 cells are targeted by pesticide exposure, we analyzed IL-17 and IL-22 serum levels in a population of 64 greenhouse workers. RESULTS AND CONCLUSION: A significant increase in IL-22 concentration was observed in serum of the exposed subjects compared to controls. These findings support the hypothesis that exposure to pesticides may reduce host defenses against infections and cancer.

Neurocognitive effects in welders exposed to aluminium.

OBJECTIVES: Various authors who studied the effects of aluminium (Al) exposure on the neurocognitive system in the last 30 years have reached different and often contradictory conclusions. The aim of this study is to help clarify the effects that the metal causes on cognitive ability in a group of naval welders exposed to Al. METHODS: The study was performed on a sample of 86 male Al welders in a shipyard in Messina. The average value of environmental Al, recorded in the workplace, was 19.5 mg/m(3). The blood levels of Al, zinc, manganese, lead and chromium were monitored in all the subjects. The reagents used for the neuropsychic study were the Wechsler Memory Scale (WMS), the Colour Word Test or Stroop Test and the Test of Attention Matrixes. The results were compared with those obtained in a similar control group not exposed to Al and with an Al-b value of 6.93 g/l. RESULTS: For all the mental reagents used, the reply is obtained in the sample of exposed subjects showed decreased cognitive response with regard to attention and memory performance. The comparison between the individual tests showed greater sensitivity of performance studied using the WMS and the Stroop Test compared with the Test of Attention Matrixes. The alterations encountered in the cognitive functions studied increased proportionally to time of exposure and quantity of metal absorbed. CONCLUSION: The study confirmed that occupational exposure to Al causes alteration in cognitive responses that are more evident in complex functions.

Serum levels of copper, selenium and manganese in forestry workers testing IgG positive for Brucella, Borrelia, and Rickettsia.

The aim of this study is to measure the alterations in the trace levels of serum copper (Cu), selenium (Se), and manganese (Mn) in forestry workers testing immunoglobulin G (IgG)-positive for Brucella, Borrelia, and Rickettsia. The study was conducted on a sample of 758 subjects (560 male and 198 female). All the subjects underwent medical examinations, which investigated particularly the presence of clinical signs compatible with zoonoses, and routine blood tests from venous blood sample, which tested previous immunisation versus cited microorganisms and serum concentration of Cu, Se, and Mn. The subjects were divided according to IgG positivity versus the cited microorganisms. The group of subjects with IgG positive versus Brucella showed statistically significant higher Cu levels than controls, while the Mn levels were not; the group of subjects with IgG positive versus Rickettsia showed higher levels of all three tested metals. The concentration of the examined metals did not show statistically significant difference between IgG-positive subjects versus subjects with Borrelia compared to controls. These data could confirm the role of both Cu and Se  in the regulation of immune response.