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Abstract Background Development of graphical/visual presentations of cancer etiology caused by environmental stressors is a process that requires combining the complex biological interactions between xenobiotics in living and occupational environment with genes (gene-environment interaction) and genomic and non-genomic based disease specific mechanisms in living organisms. Traditionally, presentation of causal relationships includes the statistical association between exposure to one xenobiotic and the disease corrected for the effect of potential confounders. Methods Within the FP6 project HENVINET, we aimed at considering together all known agents and mechanisms involved in development of selected cancer types. Selection of cancer types for causal diagrams was based on the corpus of available data and reported relative risk (RR). In constructing causal diagrams the complexity of the interactions between xenobiotics was considered a priority in the interpretation of cancer risk. Additionally, gene-environment interactions were incorporated such as polymorphisms in genes for repair and for phase I and II enzymes involved in metabolism of xenobiotics and their elimination. Information on possible age or gender susceptibility is also included. Diagrams are user friendly thanks to multistep access to information packages and the possibility of referring to related literature and a glossary of terms. Diagrams cover both chemical and physical agents (ionizing and non-ionizing radiation) and provide basic information on the strength of the association between type of exposure and cancer risk reported by human studies and supported by mechanistic studies. Causal diagrams developed within HENVINET project represent a valuable source of information for professionals working in the field of environmental health and epidemiology, and as educational material for students. Introduction Cancer risk results from a complex interaction of environmental exposures with inherited gene polymorphisms, genetic burden collected during development and non genomic capacity of response to environmental insults. In order to adopt effective preventive measures and the associated regulatory actions, a comprehensive investigation of cancer etiology is crucial. Variations and fluctuations of cancer incidence in human populations do not necessarily reflect environmental pollution policies or population distribution of polymorphisms of genes known to be associated with increased cancer risk. Tools which may be used in such a comprehensive research, including molecular biology applied to field studies, require a methodological shift from the reductionism that has been used until recently as a basic axiom in interpretation of data. The complexity of the interactions between cells, genes and the environment, i.e. the resonance of the living matter with the environment, can be synthesized by systems biology. Within the HENVINET project such philosophy was followed in order to develop interactive causal diagrams for the investigation of cancers with possible etiology in environmental exposure. Results Causal diagrams represent integrated knowledge and seed tool for their future development and development of similar diagrams for other environmentally related diseases such as asthma or sterility. In this paper development and application of causal diagrams for cancer are presented and discussed.

Abstract Nanoparticles (NPs) cause concern for health and safety as their impact on the environment and humans is not known. Relatively few studies have investigated the toxicological and environmental effects of exposure to naturally occurring NPs (NNPs) and man-made or engineered NPs (ENPs) that are known to have a wide variety of effects once taken up into an organism. A review of recent knowledge (between 2000-2010) on NP sources, and their behaviour, exposure and effects on the environment and humans was performed. An integrated approach was used to comprise available scientific information within an interdisciplinary logical framework, to identify knowledge gaps and to describe environment and health linkages for NNPs and ENPs. The causal diagram has been developed as a method to handle the complexity of issues on NP safety, from their exposure to the effects on the environment and health. It gives an overview of available scientific information starting with common sources of NPs and their interactions with various environmental processes that may pose threats to both human health and the environment. Effects of NNPs on dust cloud formation and decrease in sunlight intensity were found to be important environmental changes with direct and indirect implication in various human health problems. NNPs and ENPs exposure and their accumulation in biological matrices such as microbiota, plants and humans may result in various adverse effects. The impact of some NPs on human health by ROS generation was found to be one of the major causes to develop various diseases. A proposed cause-effects diagram for NPs is designed considering both NNPs and ENPs. It represents a valuable information package and user-friendly tool for various stakeholders including students, researchers and policy makers, to better understand and communicate on issues related to NPs.

Abstract Background Many epidemiological studies and reviews have been performed to identify the causes of bladder cancer. The aim of this review is to investigate the links between various environmental risk factors and cancer of the bladder. Methods A systematic literature search was performed using PubMed, Science Direct, Scopus, Scholar Google and Russian Google databases to identify reviews and epidemiological studies on bladder cancer risk factors associated with the environment published between 1998 and 2010. Only literature discussing human studies was considered. Results Smoking, mainly cigarette smoking, is a well known risk factor for various diseases, including bladder cancer. Another factor strongly associated with bladder cancer is exposure to arsenic in drinking water at concentrations higher than 300 µg/l. The most notable risk factor for development of bladder cancer is occupational exposure to aromatic amines (2-naphthylamine, 4-aminobiphenyl and benzidine) and 4,4'-methylenebis(2-chloroaniline), which can be found in the products of the chemical, dye and rubber industries as well as in hair dyes, paints, fungicides, cigarette smoke, plastics, metals and motor vehicle exhaust. There are also data suggesting an effect from of other types of smoking besides cigarettes (cigar, pipe, Egyptian waterpipe, smokeless tobacco and environmental tobacco smoking), and other sources of arsenic exposure such as air, food, occupational hazards, and tobacco. Other studies show that hairdressers and barbers with occupational exposure to hair dyes experience enhanced risk of bladder cancer. For example, a study related to personal use of hair dyes demonstrates an elevated bladder cancer risk for people who used permanent hair dyes at least once a month, for one year or longer. Conclusion Smoking, in particular from cigarettes, exposure to arsenic in drinking water, and occupational exposure to aromatic amines and 4,4'-methylenebis(2-chloroaniline) are well known risk factors for various diseases including bladder cancer. Although the number of chemicals related to occupational exposure is still growing, it is worth noting that it may take several years or decades between exposure and the subsequent cancer.

Abstract Although Integrated Environmental Health Monitoring (IEHM) is considered an essential tool to better understand complex environmental health issues, there is no consensus on how to develop such a programme. We reviewed four existing frameworks and eight monitoring programmes in the area of environmental health. We identified the DPSEEA (Driving Force-Pressure-State-Exposure-Effect-Action) framework as most suitable for developing an IEHM programme for environmental health impact assessment. Our review showed that most of the existing monitoring programmes have been designed for specific purposes, resulting in narrow scope and limited number of parameters. This therefore limits their relevance for studying complex environmental health topics. Other challenges include limited spatial and temporal data availability, limited development of data sharing mechanisms, heterogeneous data quality, a lack of adequate methodologies to link disparate data sources, and low level of interdisciplinary cooperation. To overcome some of these challenges, we propose a DPSEEA-based conceptual framework for an IEHM programme that would enable monitoring and measuring the impact of environmental changes on human health. We define IEHM as ‘a systemic process to measure, analyse and interpret the state and changes of natural-eco-anthropogenic systems and its related health impact over time at the same location with causative explanations across the various compartments of the cause-effect chain’. We develop a structural work process to integrate information that is based on existing environmental health monitoring programmes. Such a framework allows the development of combined monitoring systems that exhibit a large degree of compatibility between countries and regions.

Experimental and human studies describe the adverse effect of iron or vitamin B6 deficiencies on polyunsaturated fatty acid metabolism. Iron is present in end proteins of the δ6-desaturase enzyme complex, and vitamin B6 deficiency can affect the transmethylation reaction of proteins. Plasma polyunsaturated fatty acid content was estimated in apparently healthy subjects of the general population with no consumption of fish and low vitamin B6 serum levels (<3 μg/l; n = 21) or with low iron serum levels (men: <12 μmol/l; women: <10 μmol/l; n = 16) and compared to a control group (n = 22) with normal vitamin B6 and iron serum levels (in reference range). The activities of the δ6-desaturase enzyme complex were calculated as product/precursor (conversion indices). In groups of subjects with low vitamin B6 and low iron levels, δ6-desaturase activity together with δ5-desaturase activity (conversion of α-linolenic/18:3,n–3/ into eicosapentaenoic acid/20:5,n–3/) as well as the conversion index of docosahexaenoic acid formation (22:6,n–3) from 22:5,n–3 (second δ6-desaturase activity) were significantly reduced. The inhibition effect on fatty acid synthesis was more pronounced in subjects with low iron levels than in those with low vitamin B6 levels. The conversion indices correlated significantly positively with vitamin B6 or iron levels. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Because lung cells are inevitably exposed to chemicals, drugs and mineral particles, they are appropriate target cells for investigating effects of environmental toxins. We have studied alveolar macrophages and epithelial type II pneumocytes freshly isolated from the rat lung, using the comet assay to detect DNA damage (strand breaks and oxidized bases) in individual cells after treatment with pesticide paraquat. The background level of strand breaks is five times higher in freshly isolated pneumocytes than in alveolar macrophages. This difference remains even after 48 h of in vitro culture and therefore probably does not reflect trauma suffered during isolation. In contrast, endogenous formamidopyrimidine glycosylase- and endonuclease II-sensitive sites, which are specific indicators of oxidative damage, are present in freshly isolated alveolar macrophages but not in pneumocytes, reelecting the high metabolic activity of macrophages and their defensive role. Both cell types are exquisitely sensitive to strand breakage by paraquat. In addition, specific base oxidation is detected after 24 h of treatment with paraquat, especially in alveolar macrophages. Susceptibility to DNA damage rather than lipid peroxidation, is likely to be the cause of paraquat-induced death in these cells. The relatively high level of endogenous damage in pneumocytes suggests that these cells are inefficient at DNA repair, which would be consistent with their probable role as the principal progenitors of lung cancer. [ABSTRACT FROM PUBLISHER]

Among nanomaterials, silver nanoparticles (AgNPs) have the broadest and most commercial applications due to their antibacterial properties, highlighting the need for exploring their potential toxicity and underlying mechanisms of action. Our main aim was to investigate whether AgNPs exert toxicity by inducing oxidative damage to DNA in human kidney HEK 293 cells. In addition, we tested whether this damage could be counteracted by plant extracts containing phytochemicals such as swertiamarin, mangiferin and homoorientin with high antioxidant abilities. We show that AgNPs (20 nm) are taken up by cells and localised in vacuoles and cytoplasm. Exposure to 1, 25 or 100 µg/ml AgNPs leads to a significant dose-dependent increase in oxidised DNA base lesions (8-oxo-7,8-dihydroguanine or 8-oxoG) detected by the comet assay after incubation of nucleoids with 8-oxoG DNA glycosylase. Oxidised DNA base lesions and strand breaks caused by AgNPs were diminished by aqueous and methanolic extracts from both haulm and flower of Gentiana asclepiadea.

Life expectancy in central-Eastern European countries is more than 10 years lower compared with Northern or Western countries which could be the result of complex factors including genetics, nutrition and life style. We conducted a molecular epidemiological study with the aim of investigating links between DNA instability, genetic polymorphisms in nucleotide excision repair genes and ageing. Two groups-151 young people (78 women and 73 men) aged 20-25, and 140 elderly subjects (101 women and 39 men), aged 65-70 have been investigated. Results show elevated levels of micronuclei and chromosome aberrations in elderly compared with young groups (P<0.001); women had more micronuclei than men (P<0.001). Micronucleus frequencies were influenced by age (P<0.001). In the group of elderly people those who were homozygous with C/C or A/A in XPC IVS11 had more aberrant cells compared with C/A heterozygotes (P=0.04). When the dependent variable was break per cell, elderly people A/A homozygous in XPC IVS11 had more breaks per cell compared with C/A heterozygous or C/C homozygous subjects (P=0.03). Significantly the most chromatid breaks were found in elderly people both Lys/Lys homozygous in the XPD Lys751Gln genotype and C/C or A/A homozygous in the XPC IVS11 genotype (P<0.05). A General Linear Model analysis shows a statistically significant effect of interactions between age, sex and genotype XPC IVS11 (P=0.001) and age, sex and genotype XPCin9 (P=0.007) on number of chromatid breaks. When we divided people into two subgroups (without mutant allele and with one or two mutant alleles) we found a significantly higher number of chromosome exchanges in people with one or two variant polymorphism XPCin9 (P=0.04), XPC IVS11 (P=0.004) or XPCex15 (P=0.001). Level of cells with micronuclei was influenced by polymorphisms XPD Lys751Gln (P=0.03). However, we did not find any relationship between XPA polymorphism and studied cytogenetic biomarkers.