Final Activity Report Summary - EPI-TOK (Trasfer of knowledge in molecular biology and epidemiology of occupational and environmental cancer) The general aim of EPITOK transfer of knowledge project was to enhance the process of development of research activities of EPIMOL centre of excellence in advanced molecular biology and epidemiology of occupational and environmental cancer. To achieve this aim, a two-tier transfer of knowledge was implemented.The first tier included a series of visits of senior experienced researchers from six European countries to the EPIMOL centre (in total nine incoming researchers), while the second one consisted in the training of EPIMOL researchers at six different European and United States partner institutions (in total six outgoing visits). 5 training programs (TP) were conducted in order to achieve the project objectives (in total 128 PMs).Within these programs NIOM researchers have gained a highly specialised knowledge and skills in the field of:TP1. Application of novel exposure biomarkers and bio-indicators to cancer risk assessment NIOM researchers conducted in vitro studies using DNA microarrays technique, studied the activation of NF-kB transcription factor after exposure to genotoxic stress and probed the interactions between AhR and Estrogen receptor (ER) networks and their modulation by Polycyclic aromatic hydrocarbons (PAHs).TP2. Assessment of DNA damage and repair mechanisms in carcinogenesis 1 post-doc recruited to NIOM for a total of 24 PMs studied the molecular mechanisms of arsenic trioxide pro-apoptotic effects on leukemic cells (induction of oxidative stress, modulation of cellular survival responses, combined treatment with NF-B inhibitors and natural compounds).TP3. Application of cytogenetic methods for detecting changes at chromosomal level NIOM fellow gained knowledge on PCC and C-banding cytogenetic assays trying to demonstrate whether dicentric chromosomes in irradiated resting G0 human lymphocytes can trigger apoptosis.TP4. Analysis of genetic polymorphism and expression patterns of metabolising enzymes as applied to environmental carcinogenesis NIOM researcher showed that human ARNT genetic polymorphisms in the PAS region significantly reduced the transcriptional activity of CYP1A1 in Hepa c4 cells. This may suggest involvement of the polymorphisms in cancer risk modulation. In other studies, a second post-doc recruited to NIOM for 24 PMs revealed that while the expression levels of GPX1 and SEP15 did not significantly differ between healthy and tumorous lung tissues, the expression level of SEPP1 in tumorous NSCLC tissue was significantly down-regulated compared to the normal lung tissue.TP5. Performance of epidemiological studies and data analysis NIOM fellows widened their knowledge on conducting the state-of-the-art epidemiological studies through designing, performing and statistical analysis of results obtained in large epi studies in National Cancer Institute (United States), IRAS (the Netherlands) and Poland. As a result of the project NIOM young researchers: - were trained in many new modern techniques in molecular biology (e.g. assessment of gene expression by DNA microarrays, qPCR, restriction analysis of plasmids, dual luciferase reporter gene activity, gene silencing (siRNA), molecular epidemiology, and biostatistics); - strengthened scientific contacts with incoming senior scientists; - greatly improved the quality of currently conducted studies in NIOM; - published 11 papers in peer reviewed journals (4 manuscripts in preparation); - gave 2 oral presentations and presented 12 posters in international conferences and other scientific meetings; - collected numerous data and biological samples which will be used in further studies.
