Transcriptome Analysis in Peripheral Blood of Humans Exposed to Environmental Carcinogens: A Promising New Biomarker in Environmental Health Studies

BACKGROUND: Human carcinogenesis is known to be initiated and/or promoted by exposure to chemicals that occur in the environment. Molecular cancer epidemiology is used to identify human environmental cancer risks by applying a range of effect biomarkers, which tend to be nonspecific and do not generate insights into underlying modes of action. Toxicogenomic technologies may improve on this by providing the opportunity to identify, molecular biomarkers consisting of altered gene expression profiles. OBJECTIVES: The aim of the present study, was to monitor the expression of selected genes in a random sample of adults in Flanders selected from specific regions with (presumably,) different environmental burdens. Furthermore, associations of gene expression with blood and urinary, measures of biomarkers of exposure, early, phenotypic effects, and tumor markers were investigated. RESULTS: Individual gene expression of cytochrome p450 1B1, activating transcription factor 4, mitogen-activated protein kinase K superoxide dismutase 2 (Mn), chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha), diacylglycerol 0 acyltransferase homolog 2 (mouse), tigger transposable element derived 3, and PTEN-induced putative kinasel were measured by means of quantitative polymerase chain reaction in peripheral blood cells of 398 individuals. After correction for the confounding effect of tobacco smoking, inhabitants of the Olen region showed the highest differences in gene expression levels compared with inhabitants from the Gent and fruit cultivation regions. Importantly, we observed multiple significant correlations of particular gene expressions with blood and urinary, measures of various environmental carcinogens. CONCLUSIONS: Considering the observed significant differences between gene expression levels in inhabitants of various regions in Flanders and the associations of gene expression with blood or urinary measures of environmental carcinogens, we conclude that gene expression profiling appears promising as a tool for biological monitoring in relation to environmental exposures in humans

Opening the research agenda for selection of hot spots for human biomonitoring research in Belgium: a participatory research project

<p>Abstract</p> <p>Background</p> <p>In order to select priority hotspots for environment and health research in Flanders (Belgium), an open procedure was organized. Environment and health hotspots are strong polluting point sources with possible health effects for residents living in the vicinity of the hot spot. The selection procedure was part of the work of the Flemish Centre of Expertise for Environment and Health, which investigates the relation between environmental pollution and human health. The project is funded and steered by the Flemish government.</p> <p>Methods</p> <p>The involvement of other actors than merely experts is inspired by the 'analytical-deliberative' approach of the National Research Council in the United States and the extended peer community approach. These approaches stress the importance of involving different expert- and social perspectives in order to increase the knowledge base on complex issues. In the procedure used in the project a combination of expert and stakeholder input was essential. The final decision was supported by a multi-criteria analysis of expert assessment and stakeholder advice.</p> <p>Results</p> <p>The endeavour was challenging from the start because of the complicated ambition of including a diversity of actors, potential hotspots, concerns and assessment criteria, but nevertheless the procedure proved its value in both structuring and informing the decision-making process. Moreover the process gained the support of most actors participating in the process, even though the final selection could not satisfy all preferences.</p> <p>Conclusions</p> <p>Opening the research agenda exemplifies the value of inter- and transdisciplinary cooperation as well as the need for a well-structured and negotiated procedure that combines relevant factors and actors with pragmatism. The value of such a process also needs to prove itself in practice after the procedure has been completed: the tension between an ambition of openness on the one hand and a more closed attitude amongst experts on the other will continue to play a role even after closure.</p

Pollutant effects on genotoxic parameters and tumor-associated protein levels in adults: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders.</p> <p>Methods</p> <p>Subjects were 1583 residents aged 50–65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity (Calux test) were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account.</p> <p>Results</p> <p>Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p < 0.0001). Positive exposure-effect relationships were found for carcinoembryonic antigen (urinary cadmium, t,t'-muconic acid, 1-hydroxypyrene and blood lead), micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxy-deoxyguanosine (t,t'-muconic acid, 1-hydroxypyrene). Also, we found significant associations between values of PSA above the p90 and higher values of urinary cadmium, between values of p53 above the p90 and higher serum levels of p,p'-DDE, hexachlorobenzene and marker PCBs (PCB 138, 153 and 180) and between serum levels of p,p'-DDE above the p90 and higher serum values of carcinoembryonic antigen. Significant associations were also found between effect biomarkers and occupational or lifestyle parameters.</p> <p>Conclusion</p> <p>Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders.</p

Inter- and intra-annual variations of Pb/Ca ratios in clam shells (Mercenaria mercenaria): a record of anthropogenic lead pollution?

International audienceIn this study, we re-assess the use of bivalve shells as a proxy of lead pollution. Previous studies have stressed that shells display little variability compared to soft tissues and thus are better for pollution biomonitoring. However, in this manuscript we illustrate that there is large inter- and intra-annual Pb variability between shells of the clam Mercenaria mercenaria collected in North Carolina, USA. Therefore, year to year, as well as intra-annual variations in Pb/Ca ratios should be interpreted with caution. Despite this variability, we were able to obtain an annual Pb chronology from 1949 to 2002 using 11 shells collected at different times which clearly exhibited the late 1970's peak in Pb from leaded gasoline use. This indicates that when enough specimens are pooled together, bivalve shells can be used to reconstruct large, long term changes in environmental Pb concentrations. Our data compare well with other studies of aragonite clams from sites with low regional lead pollution. From this we conclude that the Cape Lookout region of North Carolina has not received extensive pollution over the 1949-2002 period. The Pb concentration in shells growing in the 1949-1976 period was not significantly different from those growing in the 1982-2002 period, although other proxies suggest that the 1949-1976 period should be considerably higher. Therefore, our data suggest that there is still a modern source of Pb in the coastal North Carolina environment

Barium uptake into the shells of the common mussel (Mytilus edulis) and the potential for estuarine paleo-chemistry reconstruction

International audienceIn this study we test if calcite shells of the common mussel, Mytilus edulis, contain barium in proportion to the water in which they grew. Similar to all bivalves analyzed to date, the [Ba/Ca]shell profiles are characterized by a relatively flat background [Ba/Ca]shell, interrupted by sharp [Ba/Ca]shell peaks. Previous studies have focused on these [Ba/Ca]shell peaks, but not on the background [Ba/Ca]shell. We show that in both laboratory and field experiments, there is a direct relationship between the background [Ba/Ca]shell and [Ba/Ca]water in M. edulis shells. The laboratory and field data provided background Ba/Ca partition coefficients (DBa) of 0.10 ± 0.02 and 0.071 ± 0.001, respectively. This range is slightly higher than the DBa previously determined for inorganic calcite, and slightly lower than foraminiferal calcite. These data suggest that M. edulis shells can be used as an indicator of [Ba/Ca]water, and therefore, fossil or archaeological M. edulis shells could be used to extend knowledge of estuarine dissolved Ba throughputs back in time. Moreover, considering the inverse relationship between [Ba/Ca]water and salinity, background [Ba/Ca]shell data could be used as an estuary specific indicator of salinity. The cause of the [Ba/Ca]shell peaks are more confusing, both the laboratory and field experiments indicate that they cannot be used as a direct proxy of [Ba/Ca]water or phytoplankton production, but may possibly be caused by barite ingestion