Allium cepa tests: A plant-based tool for the early evaluation of toxicity and genotoxicity of newly synthetized antifungal molecules.

Many fungal genera such as Aspergillus, Penicillium, Fusarium and Alternaria are able to produce, among many other metabolites, the aflatoxins, a group of toxic and carcinogenic compounds. To reduce their formation, synthetic fungicides are used as an effective way of intervention. However, the extensive use of such molecules generates long-term residues into the food and the environment. The need of new antifungal molecules, with high specificity and low off-target toxicity is worth. The aim of this study was to evaluate: i) the toxicity and genotoxicity of newly synthesized molecules with a good anti-mycotoxic activity, and ii) the suitability of the Allium cepa multi-endpoint assay as an early screening method for chemicals. Eight compounds were tested for toxicity by using the A. cepa bulb root elongation test and for genotoxicity using the A. cepa bulb mitotic index, micronuclei and chromosome aberrations tests. Three molecules showed no toxicity, while two induced mild toxic effects in roots exposed to the highest dose (100 µM). A more pronounced toxic effect was caused by the other three compounds for which the EC50 was approximately 50 µM. Furthermore, all molecules showed a clear genotoxic activity, both in terms of chromosomal aberrations and micronuclei. Albeit the known good antifungal activity, the different molecules caused strong toxic and genotoxic effects. The results indicate the suitability of experiments with A. cepa as a research model for the evaluation of the toxic and genotoxic activities of new molecules in plants before they are released into the environment.

Comparison between Macro and Trace Element Concentrations in Human Semen and Blood Serum in Highly Polluted Areas in Italy.

Macro and trace elements are important regulators of biological processes, including those ones linked to reproduction. Among them, Ca, Cu, Fe, K, Mg, Mn, Na, Se, and Zn ensure normal spermatic functions. Hence, the aim of this study was to evaluate the concentrations of 26 macro and trace elements (Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Na, Ni, Pb, Rb, Sb, Se, Sn, Sr, U, V, and Zn) in blood serum and also in semen of healthy young men, homogeneous for age, anthropometric characteristics, and lifestyle, living in three highly polluted areas in Italy. Furthermore, a comparison among three geographical areas was performed to highlight any difference in the investigated parameters and, overall, to speculate any correlations between chemical elements and semen quality. Statistically significant differences (p < 0.05) among the three areas were found for each investigated element, in both semen and serum samples, where inter-area differences were more evident in semen than in blood serum, suggesting human semen as an early environmental marker. Considering the homogeneity of three cohorts, these differences could be due more to environmental conditions in the recruiting areas, suggesting that variations in those involved in reproductive-associated pathways can have an impact on male fertility. Nevertheless, more research is needed to evaluate threshold values for sperm dysfunction and male infertility. Actually, the role of different dietary intake and environmental exposure underlying the observed differences in the recruiting areas is under further investigation for the same cohort.

Effects of a Lifestyle Change Intervention on Semen Quality in Healthy Young Men Living in Highly Polluted Areas in Italy: The FASt Randomized Controlled Trial.

BACKGROUND: Human semen quality is affected by lifestyle and environmental factors. OBJECTIVE: To evaluate the short-term effects of a diet and physical activity intervention on semen quality of healthy young men living in highly polluted areas of Italy. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial was conducted. Healthy young men were assigned to an intervention or a control group. INTERVENTION: A 4-mo Mediterranean diet and moderate physical activity program. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were sperm concentration, motility and morphology, concentration of round cells, and semen total antioxidant capacity. Secondary outcomes were adherence to Mediterranean diet and physical activity. All outcomes were measured twice, at the enrollment (t0) and at the end of the intervention (t4). RESULTS AND LIMITATIONS: A total of 263 individuals attended all visits, and underwent examinations and laboratory analyses: 137 in the intervention group and 126 in the control group. The adherence to Mediterranean diet and physical activity level increased more in the intervention group than in the control group from t0 to t4. Sperm concentration, total and progressive motility, and proportion of normal morphology cells increased in the intervention group but decreased in the control group, with statistically significant differences between the two groups at t4. The total antioxidant capacity increased in the intervention group but decreased in the control group, from t0 to t4. CONCLUSIONS: Study results showed that an intervention based on Mediterranean diet and regular physical activity can determine an improvement of semen quality in healthy young men. PATIENT SUMMARY: Our study aimed to evaluate the effect of a lifestyle intervention on semen quality of healthy young men. We assigned the 263 enrolled individuals to an intervention or a control group. The intervention group followed a 4-mo Mediterranean diet and moderate physical activity program, at the end of which the participants showed an improvement of semen quality parameters.

Genotoxic Activity of Particulate Matter and In Vivo Tests in Children Exposed to Air Pollution.

The aim of this paper was to investigate the relationship between micronuclei and DNA damage in children's buccal mucosa cells and the genotoxicity and mutagenicity of the different sized fractions of particulate matter as well as the concentration of PAHs (polycyclic aromatic hydrocarbons) and metals in particulate matter. Air particulate matter was collected by high volume samplers located near the schools attended by the children on the same days of biological samplings. The mutagenic activity was assessed in different cells in in vitro tests (Ames test on bacteria and comet test on leukocytes). Our study showed weak positive correlations between (a) the mutagenicity of the PM0.5 fraction and PAHs and (b) the micronuclei test of children's buccal cells and PAHs detected in PM0.5 and PM0.5-3 fractions. A positive correlation was also found between in vitro comet test on leukocytes and PAHs in the PM3-10 fraction. No correlation was observed for metal concentrations in each PM fraction.

The AFLATOX® Project: Approaching the Development of New Generation, Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination.

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.

Comet Test in Saliva Leukocytes of Pre-School Children Exposed to Air Pollution in North Italy: The Respira Study.

Air pollution is a well-known problem for human health, especially for children living in highly polluted urban areas. This study aimed to assess the relationship between airborne pollutants concentration and biomarkers of DNA damage in the buccal mucosa cells of pre-school children. DNA damage was investigated with comet test in saliva leukocytes taken from sputum of 3- to 6-year-old children living in Brescia, Northern Italy, collected during two consecutive winter seasons (2012-2013). The daily levels of PM10, PM2.5, NO2, CO, SO2, benzene and O3 in urban air were collected for the whole period. A questionnaire filled in by the children's parents was used to evaluate indoor and outdoor exposure. DNA damage in saliva leukocytes was evaluated in 152 children and the means of tail intensity and visual score as DNA damage were 6.2 ± 4.3 and 182.1 ± 30.9, respectively. No demographic and indoor or outdoor exposure variable was associated with the two measures of DNA damage. No significant association between air pollution and DNA damage in children's buccal leukocytes was found. In this study, the comet assay does not appear to be a valuable biomarker to detect DNA damage in children exposed to high levels of air pollutants, such as PM10, PM2.5 and NO2.

Antiaflatoxigenic Thiosemicarbazones as Crop-Protective Agents: A Cytotoxic and Genotoxic Study.

Aflatoxins are secondary fungal metabolites that can contaminate feed and food. They are a cause of growing concern worldwide, because they are potent carcinogenic agents. Thiosemicarbazones are molecules that possess interesting antiaflatoxigenic properties, but in order to use them as crop-protective agents, their cytotoxic and genotoxic profiles must first be assessed. In this paper, a group of thiosemicarbazones and a copper complex are reported as compounds able to antagonize aflatoxin biosynthesis, fungal growth, and sclerotia biogenesis in Aspergillus flavus. The two most interesting thiosemicarbazones found were noncytotoxic on several cell lines (CRL1790, Hs27, HFL1, and U937), and therefore, they were submitted to additional analysis of mutagenicity and genotoxicity on bacteria, plants, and human cells. No mutagenic activity was observed in bacteria, whereas genotoxic activity was revealed by the Alkaline Comet Assay on U937 cells and by the test of chromosomal aberrations in Allium cepa.

"Risk is in the air": Polycyclic aromatic hydrocarbons, metals and mutagenicity of atmospheric particulate matter in a town of Northern Italy (Respira study).

Air pollution has well-known harmful effects on human beings, causing both acute and chronic diseases. Some data suggest that genetic damage occurring early in life may influence the risk of having cancer and other chronic diseases in adulthood. Therefore, there is a growing interest in studying the genotoxic activity of air pollution, and especially particulate matter. The aim of this study was to analyze airborne particulate matter (PM10) collected in an industrialized town of Northern Italy. PM10 was sampled in six areas of the town, divided in three distinct dimensional classes (<0.5 µm; 0.5-3 µm and 3-10 µm), and analyzed for the quantification of polynuclear aromatic hydrocarbons and metals contents. A model-based approach using diagnostic ratios and toxic equivalency factor was also followed. Concurrently, biological assays were performed for the assessment of mutagenicity and genotoxicity in bacteria, human and plant cells. Mutagenicity was observed in bacteria and human cells, with a clear dose-response relationship, induced above all by the finest PM samples (PM0.5 and PM0.5-3), which contained the largest number of polycyclic aromatic hydrocarbons. DNA damage, such as chromosomal aberrations and micronuclei, was also found in Allium cepa root cells, but without a clear relationship with the tested doses. The in-vitro models utilized showed to be good indicators of air quality for mutagenicity. Chemical analyses evidenced high content of polycyclic aromatic hydrocarbons, metals and semi-metals in PM extracts. Polycyclic aromatic hydrocarbons, metals and mutagenicity can be ascribed mainly to vehicular traffic (in terms of both exhausted gases emission and mechanical losses), which represents a constant and ubiquitous source of human exposure, and to steel working, carried out within the urban area.

Polychlorinated biphenyl serum levels, thyroid hormones and endocrine and metabolic diseases in people living in a highly polluted area in North Italy: A population-based study.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants produced until the 1980s, which they are still present worldwide. They have been associated with metabolic and endocrine diseases and hypertension in humans, but definite evidence is lacking. A chemical factory producing PCBs caused a heavy pollution in an urban area in Northern Italy. We aimed to evaluate present PCBs serum levels according to demographic and lifestyle variables and their associations with endocrine and metabolic diseases and hypertension in the resident general population. A random sample of 816 adults aged 20-79 years (mean ± SD: 49.1 ± 16.5 years) was enrolled in a cross-sectional population-based study. The participants provided a fasting blood sample for laboratory analysis and were face-to-face interviewed about the presence of chronic diseases. The serum level of total PCBs was computed as the sum of 33 PCB congeners. The median serum level of lipid-adjusted total PCBs was 435.2 and 95th centile was 2154.9 ng/g lipid. Medium and high chlorinated PCBs with immunotoxic and endocrine disrupting activity contributed most to total PCB serum levels, particularly PCBs 138, 153, 170, 180 and 194. The serum levels of total PCBs and of PCB functional groups were positively associated with age and negatively with female gender, education, smoking habit and BMI, and not associated with serum levels of thyroid hormones and TSH and glycaemia and with presence of endocrine diseases, diabetes and hypertension by multivariable analysis. Subgroup analyses according to gender, age and BMI provided similar results. In conclusion, this study shows a long-term persistence of past exposure to PCBs and does not support the hypothesis of an association between PCB exposure and prevalence of endocrine and metabolic diseases and hypertension.

Thiosemicarbazone scaffold for the design of antifungal and antiaflatoxigenic agents: evaluation of ligands and related copper complexes.

The issue of food contamination by aflatoxins presently constitutes a social emergency, since they represent a severe risk for human and animal health. On the other hand, the use of pesticides has to be contained, since this generates long term residues in food and in the environment. Here we present the synthesis of a series of chelating ligands based on the thiosemicarbazone scaffold, to be evaluated for their antifungal and antiaflatoxigenic effects. Starting from molecules of natural origin of known antifungal properties, we introduced the thio- group and then the corresponding copper complexes were synthesised. Some molecules highlighted aflatoxin inhibition in the range 67-92% at 100 µM. The most active compounds were evaluated for their cytotoxic effects on human cells. While all the copper complexes showed high cytotoxicity in the micromolar range, one of the ligand has no effect on cell proliferation. This hit was chosen for further analysis of mutagenicity and genotoxicity on bacteria, plants and human cells. Analysis of the data underlined the importance of the safety profile evaluation for hit compounds to be developed as crop-protective agents and at the same time that the thiosemicarbazone scaffold represents a good starting point for the development of aflatoxigenic inhibitors.

A battery of assays as an integrated approach to evaluate fungal and mycotoxin inhibition properties and cytotoxic/genotoxic side-effects for the prioritization in the screening of thiosemicarbazone derivatives.

Aflatoxins represent a serious problem for a food economy based on cereal cultivations used to fodder animal and for human nutrition. The aims of our work are two-fold: first, to perform an evaluation of the activity of newly synthesized thiosemicarbazone compounds as antifungal and anti-mycotoxin agents and, second, to conduct studies on the toxic and genotoxic hazard potentials with a battery of tests with different endpoints. In this paper we report an initial study on two molecules: S-4-isopropenylcyclohexen-1-carbaldehydethiosemicarbazone and its metal complex, bis(S-4-isopropenylcyclohexen-1-carbaldehydethiosemicarbazonato)nickel (II). The outcome of the assays on fungi growth and aflatoxin production inhibition show that both molecules possess good antifungal activities, without inducing mutagenic effects on bacteria. From the assays to ascertain that the compounds have no adverse effects on human cells, we have found that they are cytotoxic and, in the case of the nickel compound, they also present genotoxic effects.

Do polychlorinated biphenyls cause cancer? A systematic review and meta-analysis of epidemiological studies on risk of cutaneous melanoma and non-Hodgkin lymphoma.

In 2015 a IARC Working Group upgraded the classification of PCBs to Group 1 "Carcinogenic to humans", also on the basis of evidence from epidemiological studies showing an excess risk for melanoma. Increased risks for non-Hodgkin lymphoma (NHL) and breast cancer were also reported though the evidence was limited. However, some recent reviews of studies on PCB exposure and risk of cancer provided discrepant findings. Therefore, we re-evaluated the association between exposure to PCBs and risk of melanoma and NHL by a systematic review and meta-analysis. We retrieved 11 independent cohort studies on occupationally exposed workers. About half of them showed increased standardized mortality or incidence ratios (SMRs or SIRs) for melanoma and none for NHL. The pooled SMRs were 1.32 (95% CI: 1.05-1.64) for melanoma and 0.94 (0.73-1.23) for NHL. Among population-based cohort and case-control studies with individual measures of PCB exposure, one only study was carried out on PCB exposure and melanoma, showing an odds ratio (OR) of 6.0 (2.0-18.2) for the highest compared to lowest quartile of PCB distribution. 13 cohort and case-control studies evaluated the association between NHL and PCB concentration in blood or subcutaneous fat, with summary OR = 1.5 (1.1-1.7) for the highest vs lowest quantile of PCB distribution. However, two cohort studies on people intoxicated by rice oil containing PCBs found no excess of deaths for skin cancer and inconsistent results for NHL. In conclusion, these findings do not provide a strong evidence that PCB exposure can increase the risk of melanoma and NHL in humans.

Lifestyles and socio-cultural factors among children aged 6-8 years from five Italian towns: the MAPEC_LIFE study cohort.

BACKGROUND: Lifestyles profoundly determine the quality of an individual's health and life since his childhood. Many diseases in adulthood are avoidable if health-risk behaviors are identified and improved at an early stage of life. The aim of the present research was to characterize a cohort of children aged 6-8 years selected in order to perform an epidemiological molecular study (the MAPEC_LIFE study), investigate lifestyles of the children that could have effect on their health status, and assess possible association between lifestyles and socio-cultural factors. METHODS: A questionnaire composed of 148 questions was administered in two different seasons to parents of children attending 18 primary schools in five Italian cities (Torino, Brescia, Pisa, Perugia and Lecce) to obtain information regarding the criteria for exclusion from the study, demographic, anthropometric and health information on the children, as well as some aspects on their lifestyles and parental characteristics. The results were analyzed in order to assess the frequency of specific conditions among the different seasons and cities and the association between lifestyles and socio-economic factors. RESULTS: The final cohort was composed of 1,164 children (50.9 boys, 95.4% born in Italy). Frequency of some factors appeared different in terms of the survey season (physical activity in the open air, the ways of cooking certain foods) and among the various cities (parents' level of education and rate of employment, sport, traffic near the home, type of heating, exposure to passive smoking, ways of cooking certain foods). Exposure to passive smoking and cooking fumes, obesity, residence in areas with heavy traffic, frequency of outdoor play and consumption of barbecued and fried foods were higher among children living in families with low educational and/or occupational level while children doing sports and consuming toasted bread were more frequent in families with high socio-economic level. CONCLUSIONS: The socio-economic level seems to affect the lifestyles of children enrolled in the study including those that could cause health effects. Many factors are linked to the geographical area and may depend on environmental, cultural and social aspects of the city of residence.

Socio-Economic and Environmental Factors Associated with Overweight and Obesity in Children Aged 6-8 Years Living in Five Italian Cities (the MAPEC_LIFE Cohort).

The prevalence of obesity among Italian children has reached such alarming levels as to require detailed studies of the causes of the phenomenon. A cross-sectional study was carried out in order to assess the weight status of 1164 Italian children aged 6-8 years (the Monitoring Air Pollution Effects on Children for Supporting Public Health Policy (MAPEC_LIFE) cohort) and to identify any associations between selected socio-economic and environmental factors and overweight/obesity. The data were obtained by means of a questionnaire given to parents, and any associations were examined by binomial logistic regression analyses. Overweight was found to be positively associated with male gender, parents of non-Italian origin, and parents who smoke, and negatively associated with the parents' level of education and employment. In addition, the frequency of overweight varied in relation to the geographical area of residence, with a greater prevalence of overweight children in the cities of central-southern Italy. This study highlights the need to implement appropriate obesity prevention programs in Italy, which should include educational measures concerning lifestyle for parents from the earliest stages of their child's life.

Occurrence and Control of Genotoxins in Drinking Water: A Monitoring Proposal.

Many studies have shown the presence of numerous organic genotoxins and carcinogens in drinking water. These toxic substances derive not only from pollution, but also from the disinfection treatments, particularly when water is obtained from surface sources and then chlorinated. Most of the chlorinated compounds in drinking water are nonvolatile and are difficult to characterize. Thus, it has been proposed to study such complex mixtures using short-term genotoxicity tests predictive of carcinogenic activity. Mutagenicity of water before and after disinfection has mainly been studied by the Salmonella/microsome (Ames test); in vitro genotoxicity tests have also been performed in yeasts and mammalian cells; in situ monitoring of genotoxins has also been performed using complete organisms such as aquatic animals or plants (in vivo). The combination of bioassay data together with results of chemical analyses would give us a more firm basis for the assessment of human health risks related to the consumption of drinking water. Tests with different genetic end-points complement each other with regard to sensitivity toward environmental genotoxins and are useful in detecting low genotoxicity levels which are expected in drinking water samples.

A Biotechnological Approach for the Development of New Antifungal Compounds to Protect the Environment and the Human Health.

BACKGROUND: In the Po Valley aflatoxins play a relevant role: the local food economy is heavily based on cereal cultivations for animal feed and human nutrition. Aims of this project are the identification of new compounds that inhibit Aspergillus proliferation, the development of new inhibitors of aflatoxins production, and the set-up a practical screening procedure to identify the most effective and safe compounds. DESIGN AND METHODS: New compounds will be synthetized with natural origin molecules as ligands and endogenous metal ions to increase their bioavailability for the fungi as metal complexes. A biotechnological high-throughput screening will be set up to identify efficiently the most powerful substances. The newly synthesized compounds with effective antifungal activities, will be evaluated with battery of tests with different end-points to assess the toxic potential risk for environmental and human health. EXPECTED IMPACT OF THE STUDY FOR PUBLIC HEALTH: The fundamental step in the project will be the synthesis of new compounds and the study of their capability to inhibit aflatoxin biosynthesis. A new, simple, inexpensive and high-throughput method to screen the anti-fungine and anti-mycotoxin activity of the new synthesised compounds will be applied. The evaluation of possible risks for humans due to toxic and genotoxic activities of the molecules will be made with a new approach using different types of cells (bacteria, plants and human cells). Significance for public healthAflatoxins contamination constitutes a health emergency because aflatoxins and mycotoxins, besides being toxic, are among the most carcinogenic substances known. Even if Aspergillus are dominant in tropical regions, recently are becoming a serious problem also in Europe and in Italy, especially in area as the Po Valley in which this problem play a particularly important role, because the local food economy is heavily based not only on cereal cultivations aimed at animal feed but also on the production of derivatives to human nutrition. The aims of this research are the development of new bioactive molecules, obtained by natural molecules and metal ions, that are able to reduce the risk of food contamination by aflatoxin, but are harmless for environmental and health and the evaluation of the newly synthesized compounds using a battery of tests with different end-points to assess the toxic potential risk for environmental and human health.

DNA damage in buccal mucosa cells of pre-school children exposed to high levels of urban air pollutants.

Air pollution has been recognized as a human carcinogen. Children living in urban areas are a high-risk group, because genetic damage occurring early in life is considered able to increase the risk of carcinogenesis in adulthood. This study aimed to investigate micronuclei (MN) frequency, as a biomarker of DNA damage, in exfoliated buccal cells of pre-school children living in a town with high levels of air pollution. A sample of healthy 3-6-year-old children living in Brescia, Northern Italy, was investigated. A sample of the children's buccal mucosa cells was collected during the winter months in 2012 and 2013. DNA damage was investigated using the MN test. Children's exposure to urban air pollution was evaluated by means of a questionnaire filled in by their parents that included items on various possible sources of indoor and outdoor pollution, and the concentration of fine particulate matter (PM10, PM2.5) and NO2 in the 1-3 weeks preceding biological sample collection. 181 children (mean age ± SD: 4.3 ± 0.9 years) were investigated. The mean ± SD MN frequency was 0.29 ± 0.13%. A weak, though statistically significant, association of MN with concentration of air pollutants (PM10, PM2.5 and NO2) was found, whereas no association was apparent between MN frequency and the indoor and outdoor exposure variables investigated via the questionnaire. This study showed a high MN frequency in children living in a town with heavy air pollution in winter, higher than usually found among children living in areas with low or medium-high levels of air pollution.

Polychlorinated biphenyls and cancer: an epidemiological assessment.

Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals produced between 1930s and 1980s primarily for insulating fluids in heavy-duty electrical equipment in power plants, industries, and large buildings. They persist in the environment and accumulate in plants and animals, and have been classified as probable carcinogens to humans. We performed a systematic review and meta-analysis of scientific literature on the relationship between PCB exposure and human cancer. Two cohorts of people highly exposed to PCBs through ingestion of contaminated rice oil and some cohorts of occupationally exposed workers failed to show a definite increase in total cancer mortality and provided inconsistent results regarding single cancers. Several cohort and case-control studies investigated the association between PCBs and specific cancers, showing an association between PCB serum levels and non-Hodgkin lymphomas (NHL), with a summary odds ratio of 1.5 (95% confidence interval: 1.1-1.7), but no consistent results for the other cancer sites and types. In conclusion, this review provides some evidence for the role of PCBs in the development of NHL, although the inconsistent results of studies performed on highly polluted people and occupationally exposed workers do not allow a firm conclusion to be drawn.

Polychlorinated biphenyls in serum, liver and adipose tissue of subjects with hepatocellular carcinoma living in a highly polluted area.

Brescia (North Italy) is located in a highly industrialized area with diffuse environmental pollution by polychlorinated biphenyls (PCBs) and with a high incidence of hepatocellular carcinoma (HCC). We aimed to investigate the concentration of PCBs congeners in serum, liver and adipose tissue of patients with HCC living in this area. We enrolled prospectively 101 HCC incident cases. Lipid-adjusted PCBs concentration of single congeners and total PCBs concentration, computed as the sum of 24 PCBs congeners, were measured in the serum of all subjects and in the liver and abdominal fat of 59 HCC cases undergoing surgery. A high correlation was found between PCBs serum and liver (Spearman r=0.79), serum and fat (r=0.91), and liver and fat (r=0.75) concentrations. Serum PCBs concentration in HCC patients did not vary according to demographical, clinical or epidemiological variables, apart from age, as PCBs concentration increased linearly with the subject's age. This study confirms that serum lipid-adjusted PCBs concentration is a valid measure of PCBs body storage and is highly correlated with PCBs concentration detected in other biological samples.

Polychlorinated Biphenyls, Glycaemia and Diabetes in a Population Living in a Highly Polychlorinated Biphenyls-Polluted Area in Northern Italy: a Cross-sectional and Cohort Study.

UNLABELLED: CONFLICTS OF INTERESTS: the authors declare no potential conflict of interests. BACKGROUND: Polychlorinated biphenyls (PCBs) have been found to be associated with diabetes in some, but not all, studies performed so far. The aim of this study was to assess the association between PCB serum levels and glycaemia and diabetes in people living in Brescia, a highly industrialised PCB-polluted town in Northern Italy. DESIGN AND METHODS: 527 subjects were enrolled in a cross-sectional population-based study: they were interviewed face-to-face in 2003 and also provided a blood sample under fasting conditions. The concentration of 24 PCB congeners was determined using gas-chromatography (GC/MS). Subsequently, all subjects were included in a follow-up (cohort) study. According to the Local Health Authority health-care database, subjects were considered to be diabetic if they had diabetes at interview time (prevalent cases) or during a 7-year follow-up (incident cases). RESULTS: A total of 53 subjects (10.0%) were diabetics: 28 had diabetes at enrolment and other 25 developed the disease subsequently. Diabetes frequency increased according to the serum concentrations of total PCBs and single PCB congeners, but no association was found when estimates were adjusted for education, body mass index, age and gender by logistic regression analysis. Accordingly, glycaemia increased with PCB serum levels, but no association was observed when multiple regression analysis, including confounding factors, was performed. CONCLUSIONS: This study does not support the hypothesis that PCB environmental exposure is strictly associated with diabetes or glycaemia.