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NEWGENERIS Résumé de rapport

Project ID: 16320
Financé au titre de: FP6-FOOD
Pays: Netherlands

Final Report Summary - NEWGENERIS (Development and application of biomarkers of dietary exposure to genotoxic and immunotoxic chemicals and of biomarkers of early effects …)

The ultimate aim of the NEWGENERIS project was to investigate the role of prenatal and early-life exposure to genotoxic chemicals present in food and the environment in the development of childhood cancer and immune disorders. Specifically, the project studied the maternal exposure during pregnancy to selected carcinogenic and immunotoxic chemicals and evaluated the resulting fetal (in utero) exposure and its effects on the fetus and in later childhood, particularly in relation with childhood cancer and immune disorders. The hypothetical role of the relevant exposures of the fathers was also evaluated.

The main research tool employed by NEWGENERIS was the biomarkers, i.e. chemicals or cellular components measured in human fluids or tissues, indicative of exposure to toxic chemicals or of their early biological effects. In the context of the project, such biomarkers were measured in biological samples (venous blood from the mothers, venous blood and semen from a limited number of fathers, and umbilical cord blood from the newborns) available in mother-child birth cohorts / biobanks in Norway, Denmark, United Kingdom, Spain and Greece. In addition, childhood leukemia (ALL) cases would be recruited from the internationally unique Berlin-Frankfurt-Münster study in Germany, and evaluated for relevant genetic polymorphisms. The combination of these cohorts comprised a total of around 250 000 mother-child pairs, thus enabling a substantial molecular epidemiology study.

The specific objectives of NEWGENERIS were the following:
1. dietary exposure of pregnant women to dietary carcinogens and immunotoxins were assessed using available questionnaires from existing mother-child birth cohorts;
2. epidemiological surveys of mother-child birth cohorts were used to study associations between maternal dietary exposure and childhood cancer risk factors and immune disorders;
3. paternal exposure to dietary toxins was considered as an additional genetic risk;
4. an in vitro model of transplacental perfusion was used to better understand in utero exposure to selected toxins;
5. in cord blood samples from existing cohorts and newly initiated biobanks biomarkers were used to assess fetal exposure to these compounds and compared with maternal exposure;
6. the same samples, genetic pathways indicative of risks of cancer and immune disorders in later childhood were studied by analysis of lymphocytic gene expression and proteomics profiles;
7. inter-individual variability in responses were evaluated by genotyping of infants' DNA, and by phenotyping for DNA-repair activities;
8. Overall public health implications as well as ethical issues, would be addressed;
9. the results were disseminated to European Union (EU) food industry, advisors, regulators, and consumer organisations. Training and educational activities were carried out.

The following interactions between the Research and technological development (RTD) lines were pivotal for the progress and integration of the investigations:
- In the first place, during the preparatory phase of this project, the partners reached consensus on a shortlist of the most relevant dietary genotoxins and immunotoxins. This list comprised model compounds representing the most relevant sources of toxic contaminations hampering food safety, as well as optimally representing the chosen classes of toxicity, namely carcinogenesis and immunotoxicity. It also included agents for which epidemiological or toxicological data raised concerns of possible involvement in the causation of human disease.
- In the preparatory phase of NEWGENERIS, it was calculated that the volume of blood required for all biomarker analyses was too much to be delivered by a single mother. This implied that blood samples from multiple children were required for analysing the full range of foreseen biomarkers of exposure, effect and susceptibility. The availability of large population samples with well characterised exposures from the birth cohorts allowed the identification of subgroups with sufficient subjects to allow the completion of all analyses. The biomarkers to be analysed in specific sub-cohorts would be therefore selected on the basis of available exposure information.

In the second place, given the limitations on the amount of biological material available from humans, especially newborns, obtained samples were of high value, and had to be taken, transported and stored with great care in order to allow reliable biomarker analyses. Biological specimens were sampled, stored within particular Work packages (WPs), and subsequently transported for investigation under other WPs. To guarantee scientific quality, white blood cells should be isolated, frozen and stored under exact conditions. For this purpose, standard protocols on sample handling were set up and validated, and were consistently applied by the relevant WPs. Although features differ, the same holds true for data handling. Therefore, also with respect to data sampling, warehousing, and, subsequently centralisation of data suitable for statistical analyses, standard research protocols were devised, in particular within WP12, and applied within other WPs. This required effective internal communication between WP leaders and partners which was concisely supervised by NEWGENERIS management under WP17.

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