INSTITUTE OF BIOLOGY, MEDICINAL CHEMISTRY & BIOTECHNOLOGY
 
  Drug Discovery
  Molecular Analysis
  Organic and Organometallic Chemistry
  Medicinal Chemistry
  Structural Biology & Chemistry
  Molecular Endocrinology
  Signal Mediated Gene Expression
  Molecular & Cellular Ageing
  Biomedical Applications
  Holistic Approaches in Health
  Chemical Carcinogenesis and Genetic Toxicology
  Metabolic Engineering-Bioinformatics
  Biotechnology
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology

 

Chemical Carcinogenesis and Genetic Toxicology

 

 

 

Research Team

Dr. Soterios A. Kyrtopoulos, Research professor

Dr. Vasilis L. Souliotis, Research Associate Professor
Dr. Vassiliki Pletsa, Research Assistant Professor
Dr. Panagiotis Georgiadis, Research Associate Professor
Dr. Maria Botsivali, Research Associate
Margarita Bekyrou, Research Technician
Stella Kaila , Research Technician
Irene Kolonti, Technician
Hara Episkopou, Biologist, Ph.D. student
Dimitra Stephanou, M.D., Ph.D. student

Top

Research objectives

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.

Top

Applied research and consultancy services

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

Top

Existing or recent competitive Research Grants

1. EXPOsOMICS: http://www.exposomicsproject.eu/  EU FP7 Integrated Project, 2012-2016. European network with 12  parnters; coordinator: P. Vineis, Imperial college, London; NHRF budget (EU contribution): 350.000 euro

The exposome concept refers to the totality of environmental exposures from conception onwards, and is a novel approach to studying the role of the environment in human disease.

The EXPOsOMICS project aims to predict individual disease risk related to the environment, by characterizing the external and internal exposome for common exposures (air and drinking water contaminants) during critical periods of life, including in utero. Using ‘omic’ techniques the collected exposure data can be linked to biochemical and molecular changes in our body. The results will help to improve our understanding on how these pollutants influence the risk of developing chronic diseases. 

 

2. ''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 EnvioGenomarkers 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

3. ''Environmental Cancer, Nutrition and Individual Susceptibility'' (ECNIS): EU FP6 Network of Excellence, 2005-2009; co-ordinator: Dr. K. Rydzynski, NOFER Institute, Lodz, Poland; NHRF budget for first 24 months: 493.042 euro)

ECNIS is a Network of Excellence in the context of which some of the top 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

ΕCNIS Newsletter No. 8

4. ''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

NewGeneris Newsletter No. 2/3

 

Top

Selected recent publications

 

 

 

Recent publications (2007-2013)

1: Vafeiadi M, Vrijheid M, Fthenou E, Chalkiadaki G, Rantakokko P, Kiviranta H,Kyrtopoulos SA, Chatzi L, Kogevinas M. Persistent organic pollutants exposure during pregnancy, maternal gestational weight gain, and birth outcomes in themother-child cohort in Crete, Greece (RHEA study). Environ Int. 2014 Jan 2;64C:116-123. doi: 10.1016/j.envint.2013.12.015. [Epub ahead of print]

2: Gkotzamanidou M, Christoulas D, Souliotis VL, Papatheodorou A, Dimopoulos MA,  Terpos E. Angiogenic cytokines profile in smoldering multiple myeloma: No difference compared to MGUS but altered compared to symptomatic myeloma. Med Sci  Monit. 2013 Dec 20;19:1188-94. doi: 10.12659/MSM.889752.

3: Kelly RS, Lundh T, Porta M, Bergdahl IA, Palli D, Johansson AS, Botsivali M, Vineis P, Vermeulen R, Kyrtopoulos SA, Chadeau-Hyam M; EnviroGenoMarkers project  consortium. Blood Erythrocyte Concentrations of Cadmium and Lead and the Risk of  B-Cell Non-Hodgkin's Lymphoma and Multiple Myeloma: A Nested Case-Control Study.
PLoS One. 2013 Nov 28;8(11):e81892. doi:10.1371/journal.pone.0081892.

4: Merlo DF, Agramunt S, Anna L, Besselink H, Botsivali M, Brady NJ, Ceppi M, Chatzi L, Chen B, Decordier I, Farmer PB, Fleming S, Fontana V, Försti A, FthenouE, Gallo F, Georgiadis P, Gmuender H, Godschalk RW, Granum B, Hardie LJ, Hemminki K, Hochstenbach K, Knudsen LE, Kogevinas M, Kovács K, Kyrtopoulos SA, Løvik M,Nielsen JK, Nygaard UC, Pedersen M, Rydberg P, Schoket B, Segerbäck D, Singh R,Sunyer J, Törnqvist M, van Loveren H, van Schooten FJ, Vande Loock K, von Stedingk H, Wright J, Kleinjans JC, Kirsch-Volders M, van Delft JH. Micronucleiin Cord Blood Lymphocytes and Associations with Biomarkers of Exposure toCarcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression: The NewGeneris Cohort. Environ Health Perspect. 2013 Nov 19.

5: Papadodima O, Chatziioannou A, Patrinou-Georgoula M, Kolisis FN, Pletsa V, Guialis A. HuR-regulated mRNAs associated with nuclear hnRNP A1-RNP complexes. Int J Mol Sci. 2013 Oct 11;14(10):20256-81. doi: 10.3390/ijms141020256.

6: Gkotzamanidou M, Terpos E, Bamia C, Kyrtopoulos SA, Sfikakis PP, Dimopoulos MA, Souliotis VL. Progressive changes in chromatin structure and DNA damage response signals in bone marrow and peripheral blood during myelomagenesis. Leukemia. 2013 Oct 3. doi: 10.1038/leu.2013.284.

7: Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Törnqvist M, Sunyer J, Nielsen JK, Merlo DF, Mendez MA, Meltzer HM, Lukács V, Landström A, Kyrtopoulos SA, Kovács K, Knudsen LE, Haugen M, Hardie LJ, Gützkow KB, Fleming S,Fthenou E, Farmer PB, Espinosa A, Chatzi L, Brunborg G, Brady NJ, Botsivali M, Arab K, Anna L, Alexander J, Agramunt S, Kleinjans JC, Segerbäck D, Kogevinas M.
Bulky dna adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris). Environ Health Perspect. 2013 Oct;121(10):1200-6. doi: 10.1289/ehp.1206333.

8: Kyrtopoulos SA. Making sense of OMICS data in population-based environmental health studies. Environ Mol Mutagen. 2013 Aug;54(7):468-79. doi:10.1002/em.21778.

9: Hebels DG, Georgiadis P, Keun HC, Athersuch TJ, Vineis P, Vermeulen R,Portengen L, Bergdahl IA, Hallmans G, Palli D, Bendinelli B, Krogh V, Tumino R,Sacerdote C, Panico S, Kleinjans JC, de Kok TM, Smith MT, Kyrtopoulos SA; EnviroGenomarkers Project Consortium. Performance in omics analyses of blood samples in long-term storage: opportunities for the exploitation of existing biobanks in environmental health research. Environ Health Perspect. 2013
Apr;121(4):480-7. doi: 10.1289/ehp.1205657.

10: Pedersen M, von Stedingk H, Botsivali M, Agramunt S, Alexander J, Brunborg G, Chatzi L, Fleming S, Fthenou E, Granum B, Gutzkow KB, Hardie LJ, Knudsen LE, Kyrtopoulos SA, Mendez MA, Merlo DF, Nielsen JK, Rydberg P, Segerbäck D, Sunyer J, Wright J, Törnqvist M, Kleinjans JC, Kogevinas M; NewGeneris Consortium. Birth weight, head circumference, and prenatal exposure to acrylamide from maternal
diet: the European prospective mother-child study (NewGeneris). Environ Health Perspect. 2012 Dec;120(12):1739-45. doi: 10.1289/ehp.1205327

11: Stefanou DT, Episkopou H, Kyrtopoulos SA, Bamias A, Gkotzamanidou M, Bamia C, Liakou C, Bekyrou M, Sfikakis PP, Dimopoulos MA, Souliotis VL. Development and validation of a PCR-based assay for the selection of patients more likely to benefit from therapeutic treatment with alkylating drugs. Br J Clin Pharmacol.
2012 Nov;74(5):842-53. doi: 10.1111/j.1365-2125.2012.04274.x.

12: Georgiadis P, Kovács K, Kaila S, Makedonopoulou P, Anna L, Poirier MC, Knudsen LE, Schoket B, Kyrtopoulos SA. Development and validation of a direct sandwich chemiluminescence immunoassay for measuring DNA adducts of benzo[a]pyrene and other polycyclic aromatic hydrocarbons. Mutagenesis. 2012 Sep;27(5):589-97. doi: 10.1093/mutage/ges024.

13: Georgiadis P, Polychronaki N, Kyrtopoulos SA. Progress in high-throughput assays of MGMT and APE1 activities in cell extracts. Mutat Res. 2012 Aug1;736(1-2):25-32. doi: 10.1016/j.mrfmmm.2012.05.002.

14: Hebels DG, Brauers KJ, van Herwijnen MH, Georgiadis PA, Kyrtopoulos SA, Kleinjans JC, de Kok TM. Time-series analysis of gene expression profiles induced by nitrosamides and nitrosamines elucidates modes of action underlying their genotoxicity in human colon cells. Toxicol Lett. 2011 Dec 15;207(3):232-41. doi:
10.1016/j.toxlet.2011.09.012.

15: Koryllou A, Patrinou-Georgoula M, Dimozi A, Kyrtopoulos SA, Pletsa V. Investigation of cell death induced by N-methyl-N-nitrosourea in cell lines of human origin and implication of RNA binding protein alterations. Anticancer Res.  2011 Dec;31(12):4291-9. PubMed PMID: 22199294.

16: Georgiadis P, Kaila S, Makedonopoulou P, Fthenou E, Chatzi L, Pletsa V, Kyrtopoulos SA. Development and validation of a new, sensitive immunochemical assay for O?-methylguanine in DNA and its application in a population study. Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):82-90. doi: 10.1158/1055-9965.EPI-10-0788

17: Koryllou A, Patrinou-Georgoula M, Troungos C, Pletsa V. Cell death induced by N-methyl-N-nitrosourea, a model S(N)1 methylating agent, in two lung cancer cell  lines of human origin. Apoptosis. 2009 Sep;14(9):1121-33. doi: 10.1007/s10495-009-0379-x.

18: Episkopou H, Kyrtopoulos SA, Sfikakis PP, Fousteri M, Dimopoulos MA, Mullenders LH, Souliotis VL. Association between transcriptional activity, local  chromatin structure, and the efficiencies of both subpathways of nucleotide excision repair of melphalan adducts. Cancer Res. 2009 May 15;69(10):4424-33. doi: 10.1158/0008-5472.CAN-08-3489.

19: Sotiroudis TG, Kyrtopoulos SA. Anticarcinogenic compounds of olive oil andrelated biomarkers. Eur J Nutr. 2008 May;47 Suppl 2:69-72. doi:10.1007/s00394-008-2008-9. Review.

20: Akesson B, Kyrtopoulos SA. Compounds in food. Eur J Nutr. 2008 May;47 Suppl 2:1-2. doi: 10.1007/s00394-008-2002-2.

21: Dimopoulos MA, Souliotis VL, Anagnostopoulos A, Bamia C, Pouli A, Baltadakis  I, Terpos E, Kyrtopoulos SA, Sfikakis PP. Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma. Haematologica. 2007 Nov;92(11):1505-12.

22: Sarrif A, Wiegand HJ, Knudsen LE, Kyrtopoulos SA, Srám RJ, Vrijhof H. Biomarkers in children and adults-Introduction and overview. Toxicol Lett. 2007 Jul 30;172(1-2):1-3. Epub 2007 May 25.

23: Sfikakis PP, Souliotis VL, Fragiadaki KG, Moutsopoulos HM, Boletis JN, Theofilopoulos AN. Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin Immunol. 2007 Apr;123(1):66-73. Epub 2007 Jan 31..

24: Sarrif A, Kyrtopoulos SA, Autrup H, Farmer P, Kirsch-Volders M, Kleinjans JC,Knudsen LE, Mathar U, Wiegand HJ, Vrijhof H. Environmental genotoxins in children and adults: introduction and overview. Mutat Res. 2006 Sep 28;608(2):97-9. Epub 2006 Jul 11.

Top

 
EU projects

 

 
      
 

 

Programme News

 

 

 

 
 

 

   
       

 

 

© National Hellenic Research Foundation (NHRF), 48 Vassileos Constantinou Ave., 11635 Athens, Greece, Tel. +302107273700, Fax. +302107246618