Dr. Vasilis L. Souliotis, Research Associate Professor Dr. Vassiliki Pletsa, Research Assistant Professor (temporarily seconded to the General Secretariat for Resesarch and Technology) Dr. Panagiotis Georgiadis, Research Assistant Professor Dr. Dimitris Stellas, Research Associate Dr. Eleni Makrinou, Research Associate Dr. Maria Botsivali, Research Associate Margarita Bekyrou, Research Technician
Stella Kaila , Research Technician Irene Kolonti, Technician Hara Episkopou, Biologist, Ph.D. student Evi Makedonopoulou, Biologist, Ph.D. student Dimitra Stephanou, M.D., Ph.D. student
Research within the Program of Chemical Carcinogenesis and Genetic Toxicology focuses on two inter-related directions:
a) Mechanisms of chemical carcinogenesis and genetic toxicity
Within this direction, we investigate the mechanisms of carcinogenesis by chemical or physical agents of environmental relevance, focusing particularly on the study of DNA damage, its repair and cellular responses to it, as well as their modulation by dietary factors. We also examine the role of DNA damage and repair induced by alkylating drugs employed in cancer chemotherapy.
b) Gene-environment interactions in carcinogenesis
Within this direction we work on the development of biomarkers of exposure and genetic susceptibility to carcinogens and their application in population studies, aiming at the elucidation of the role of environmental and dietary agents in the modulation of cancer risk. Particular attention is paid to the exploitation in this area of the potential of genomics technologies.
The overall aim of our work is to achieve an integration of mechanistic and biomarker-based studies, a) to support mechanism-based cancer risk assessment and b) to facilitate the development of individualized chemotherapy protocols.
The main ongoing activities of the Team include:
the development, using genomics technologies, especially epigenomics, of new biomarkers with disease risk-predictive ability and their application in the context of large-scale population studies to the investigation of the role of a range of environmental agents in the causation of cancer in adults as well as of neurodevelopmental and immune diseases in children. Currently our main tool for these studies is the European Integrated Project EnviroGenomarkers which we coordinate;
the application, in the context of population studies, of validated biomarkers of exposure to dietary and environmental agents to study the role of a) the exposure of pregnant women in the risk of appearance of cancer and other diseases during the early life of their children, and b) the exposure of adults to dietary and environmental agents in the causation of various types of cancer. These studies are being conducted in the context of the European projects NewGeneris and ECNIS, respectively;
the study of the mechanisms of repair of DNA damage caused by genotoxic agents of environmental and pharmaceutical relevance;
the development and application of biomarkers, based on the ability to repair DNA damage, for the prediction of clinical responses, at the individual level, of cancer patients undergoing chemotherapy with genotoxic drugs, with the ultimate objective of developing individualized therapeutic protocols.
The Unit of Environmental Toxicology provides consultancy services in areas related to the effects of the environment (including food) on health, in particular in connection with risk assessment regarding dangerous substances in food and the environment to support policy development.
Responsible scientist:
Dr. M. Botsivali
Tel: 210-7273784
email: mbotsi
1. ''Genomics biomarkers of environmental health'' (EnviroGenomarkers): EU FP7 Integrated Project, 2009-2013. European network with 11 parnters; coordinator: S.A. Kyrtopoulos; NHRF budget (EU contribution): 474.000 euro
EnvioGenomarkers is a prospective molecular epidemiology study nested within 3 population cohorts / biobanks: EPIC Italy, the Northern Sweden Health and Disease Study and the Rhea mother-child cohort in Crete. Biosamples from subjects with or without disease (breast cancer, B-cell lymphoma, children with neurodevelopmental or immune diseases), collected prior to development of disease, are being examined with the aim of discovering biomarkers with the ability to predict future disease risk and of evaluating their association with exposure to a range of toxic agents of environmental and food origin (PCB, PAH, cadmium, phthalates and others). The search for biomarkers is based primarily on the extensive use of –omics technologies, including transcriptomics, metabolomics, proteomics and epigenomics. This is the first, large-scale European molecular epidemiology study that relies mainly on these new technologies. The NHRF team, in addition to co-ordinating the project, is responsible for conducting epigenomic analyses and contributes to activities related to DNA damage measurement and dietary exposure assessment. It is also in charge of the Communication and Dissemination Office of the project. More information about ECNIS can be obtained by contacting
Dr. Maria Botsivali,
EnviroGenomarkers Science Communication and Dissemination Officer,
National Hellenic Research Foundation
tel.: +30-210-7273784
fax: +30-210-7273677
email: mbotsi
ECNIS is a Network of Excellence in the context of which some of the tope European resarch teams in the area of environmental carcinogenesis work together with the objective of the creation of a strong and lasting network of research on the environmental causes of cancer and their interaction with genetics and nutrition, using mainly methodologies based on biomarkers and molecular epidemiology. The contributions of the NHRF team to ECNIS activities include, among others, the coordination of the Science Monitoring and Review Taskforce as well as the operation of the Network/s Science Communication and Dissemination Office. More information about ECNIS can be obtained by contacting
Dr.. Maria Botsivali,
ECNIS Science Communication and Dissemination Officer,
National Hellenic Research Foundation
tel.: +30-210-7273784
fax: +30-210-7273677
email: mbotsi
3. ''Newborns and Genotoxic exposure risks'' (NewGeneris, EU FP6 Integrated Project; 2005-2009; co-ordinator: Dr. J. Kleinjans, University of Maastricht, Netherlands; NHRF budget, 50% EC contribution: 375.000 euro)
NewGeneris is a European Integrated Project studying the relationship between exposure, during gestation (via the pregnant mother) or early childhood, to toxic chemicals in the environment and food, and the appearence of cancer or immune disease (e.g. asthma, allergic rinoconjuctivities) in childood or later life. For this purpose experimental methodologies are employed, as well as methodologies based on biomarkers and molecular epidemiology among selected population groups from different European regions covering a wide spectrum of exposures, nutritional habits and genetic backgrounds (Norway, Denmark, United Kingdom, Germany, Spain, Greece). Twenty five research groups, coming from 16 countries, participate in the project. The NHRF team/s contribution includes the co-ordination of exposure assessment activities, investigations of biomarkers of carcinogen exposure and of individual ability to repair carcinogen-induced DNA damage, as well as the operation of the project Network/s Communication Office. More information can be obtained by contacting
Dr. Maria Botsivali,
NewGeneris Science Communication Officer,
National Hellenic Research Foundation
tel.: 210-7273784
fax: 210-7273677
email: mbotsi
Episkopou H., Kyrtopoulos S.A., Sfikakis P.P., Fousteri M., Dimopoulos M.A., Mullenders L.H.F. and Souliotis V.L. (2009) Association between transcriptional activity, local chromatin structure and the efficiencies of both subpathways of nucleotide excision repair of melphalan adducts. Cancer Res. 69, 4424-4433
Merlo, D.F., Wild, C.P., Kogevinas, M., Kyrtopoulos, S., Kleinjans, J., NewGeneris Consortium (2009) NewGeneris: a European study on maternal diet during pregnancy and child health. Cancer Epidemiol Biomarkers Prev. 18, 5-10.
Gallo, V., Khan, A., Gonzales, C., Phillips, D.H., Schoket, B., Gyorffy, E., Anna. L, Kovacs, K., Moller, P., Loft, S., Kyrtopoulos, S., Matullo, G. and Vineis, P. (2008) Validation of biomarkers for the study of environmental carcinogens: a review. Biomarkers 13, 505-534.
Sotiroudis, T.G. and Kyrtopoulos, S.A. (2008) Anticarcinogenic compounds of olive oil and related biomarkers. Eur. J. Nutr. 47, Suppl 2, 69-72.
Akesson, B. and Kyrtopoulos, S.A. (2008) Biomarkers of exposure to and mechanisms behind the anticarcinogenic action of selected dietary components. Introduction. Eur. J. Nutr. 47, Suppl. 2, 1-2.
Dimopoulos, M.A., Souliotis, V.L., Anagnostopoulos, A., Bamia, C., Pouli, A., Baltadakis,
I., Terpos, E,, Kyrtopoulos, S.A. and Sfikakis, P.P. (2007) Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma. Haematologica 92, 1505-12.
Sarrif A, Wiegand HJ, Knudsen LE, Kyrtopoulos SA, Sram RJ, Vrijhof H. (2007) Biomarkers in children and adults-Introduction and overview. Toxicol Lett. 172, 1-3.
Sarrif A, Kyrtopoulos SA, Autrup H, Farmer P, Kirsch-Volders M, Kleinjans JC, Knudsen LE, Mathar U, Wiegand HJ, Vrijhof H. (2006) Environmental genotoxins in children and adults: introduction and overview. Mutat Res. 608, 97-9.
Sarrif A, Kyrtopoulos SA, Rydzinski KJ, Bartsch H. (2006) Environmental genotoxins in children and adults: concluding remarks. Mutat Res. 608, 169-70.
Kyrtopoulos SA, Sarrif A, Elliott BM, Schoket B, Demopoulos NA. (2006) Biomarkers and molecular epidemiology--present state and future trends: concluding remarks. Mutat Res. 600, 77-8.
Biomarkers and molecular epidemiology--present state and future trends (Special Editors: A. Sarrif and S.A. Kyrtopoulos), Mutat. Res. 600 (1-2) (2006), 1-206.
Environmental Genotoxins in Children and Adults (Special Editors: A. Sarrif and S.A. Kyrtopoulos), Mutat. Res. 608 (2) (2006), 97-170.
Souliotis, V.L., Dimopoulos, M.A., Episkopou, H.G., Kyrtopoulos, S.A. and Sfikakis, P.P. (2006)
Preferential in vivo DNA repair of melphalan-induced damage in human genes is greatly affected by the local chromatin structure. DNA Repair (Amst)., 5, 972-85.
Singh, R., Gaskell, M., Le Pla, R.C., Kaur, B., Azim-Araghi, A., Roach, J., Koukouves, G.,
Souliotis, V.L., Kyrtopoulos, S.A. and Farmer, P.B. (2006) Detection and quantitation of benzo[a]pyrene-derived DNA adducts in mouse liver by liquid chromatography-tandem mass spectrometry: comparison with 32P-postlabeling. Chem Res Toxicol., 19, 868-78.
Topinka, J., Loli, P., Hurbakova, M., Kovacikova, Z., Volkovova, K., Wolff, T., Oesterle,
D., Kyrtopoulos, S.A. and Georgiadis, P. (2006) Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats. Mutat Res., 595, 167-73.
Topinka, J., Loli, P., Dusinska, M., Hurbankova, M., Kovacikova, Z., Volkovova, K., Kazimirova, A., Barancokova, M., Tatrai, E., Wolff, T., Oesterle, D., Kyrtopoulos, S.A. and Georgiadis, P. (2006) Mutagenesis by man-made mineral fibres in the lung of rats. Mutat Res., 595, 174-83.
Pletsas, D., Wheelhouse, R.T., Pletsa, V., Nicolaou, A., Jenkins, T.C., Bibby, M.C. and Kyrtopoulos, S.A. (2006) Polar, functionalized guanine-O6 derivatives resistant to repair by
O6-alkylguanine-DNA alkyltransferase: implications for the design of DNA-modifying drugs.
Eur. J. Med. Chem., 41, 330-9.
Kyrtopoulos, S.A. (2006) Biomarkers in environmental carcinogenesis research: striving for a new momentum. Toxicol Lett., 162, 3-15.
Ayi Fanou, L., Mobio, T.A., Creppy, E.E., Fayomi, B., Fustoni, S., Moller, P., Kyrtopoulos,
S., Georgiades, P., Loft, S., Sanni, A., Skov, H., Ovrebo, S. and Autrup, H. (2006) Survey of air pollution in Cotonou, Benin--air monitoring and biomarkers. Sci. Total Environ., 358, 85-96.
Dimopoulos, M.A., Souliotis, V.L., Anagnostopoulos, A., Papadimitriou, C. and Sfikakis, P.P. (2005) Extent of Damage and Repair in the p53 Tumor-Suppressor Gene After Treatment of Myeloma Patients With High-Dose Melphalan and Autologous Blood Stem-Cell Transplantation Is Individualized and May Predict Clinical Outcome. J Clin Oncol., 23, 4381-9.
Georgiadis, P., Topinka, J., Vlachodimitropoulos, D., Stoikidou, M., Gioka, M., Stephanou, G., Autrup, H., Demopoulos, N.A., Katsouyianni, K., Sram, R. and Kyrtopoulos, S.A. (2005), Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts. Carcinogenesis, 26, 93-101.
Souliotis, V.L., Sfikakis, P.P., Anderson, L.M. and Kyrtopoulos, S.A. (2004) Intra and intercellular variations in the repair efficiency of O6 methylguanine, and their contribution to kinetic heterogeneity. Mutat. Res., 568, 155-170.
Topinka, J., Loli, P., Georgiadis, P., Dusinska, M., Hurbankova, M., Kovacikova, Z., Volkovovad, K., Kazimirova, A., Barancokova, M., Tatrai, E., Oesterle, D., Wolff, T. and Kyrtopoulos, S.A. (2004) Mutagenesis by asbestos in the lung of lambda lacI transgenic rats. Mutat. Res., 553, 67-78.
Loli, P., Topinka, J., Georgiadis, P., Dusinska, M., Hurbankova, M., Kovacikova, Z., Volkovovad, K., Wolff, T., Oesterle, D. and Kyrtopoulos, S.A. (2004) Benzo[a]pyrene-enhanced mutagenesis by asbestos in the lung of lambda-lacI transgenic rats. Mutat. Res., 553, 79-90.
Dusinska, M., Collins, A., Kazimirova, A., Barancokova, M., Harrington, V., Volkovova, K., Staruchova, M., Horska, A., Wsolova, L., Kocan, A., Petrik, J., Machata, M., Ratcliffe, B. and Kyrtopoulos, S.A. (2004) Genotoxic effects of asbestos in humans. Mutat. Res., 553, 91-102.
Tulinska J., Jahnova E., Dusinska M., Kuricova M., Liskova A., Ilavska S., Horvathova M., Wsolova L., Kyrtopoulos S.A., Collins A., Harrington V. and Fuortes L. (2004), Immunomodulatory effects of mineral fibres in occupationally exposed workers. Mutat. Res., 553, 111-124.
Current EU projects 
