The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

FP6 priority
1.1.1   Genomics and Biotechnology for Health
Title of the proposal

Modulation of carcinogenic effects of chemicals by antioxidants; study on mammalian cells in vitro and ex vivo

Slovak Academy of Sciences, Cancer Research Institute (CRI)
Vlarska 7, 83391 Bratislava, Slovak Republic
+421 2 59327203

Research subject for a potential FP6 project

There is now considerable evidence that a high intake of fruit and vegetables can decrease the risk of cancer. While it is not clear how this particular diet alters cancer risk, there is substantial metabolic and experimental evidence to implicate antioxidant micronutrients. The complex process of carcinogenesis comprises at least tree main steps: initiation, promotion and progression. Oxidative stress induced by different environmental and internal factors may participate in all steps of carcinogenesis. Endogenously produced and exogenously administered antioxidants are molecules that either directly or indirectly detoxify free radicals of reactive oxygen spesies (ROS) and thus may protect against cancer. Antioxidants may act at different steps of carcinogenesis. We plan to investigate the role of natural antioxidants (vitamins and other micronutrients as lignins, glucans, rosemary) in the initiation phase of carcinogenesis. This phase represents a mutation in the primary structure of DNA which activates an oncogene or inhibits antioncogene (tumor supressor gene). We will estimate by cytogenetic, biochemical, and fluorescent methods reduction of genotoxic effects of several carcinogens and modulation of DNA repair by antioxidants. In mammalian cells cultured in vitro (human cells) and ex vivo (freshly isolated rat hepatocytes or rat testicular cells) we will study protective effects of natural antioxidants from different standpoints: the extent of cytogenetic changes, the extent of damage and repair of total DNA, gene-specific repair of tumor supressor gene p53. We will study specificity of the protective effects with respect to the chemical nature of DNA damage (DNA breaks, oxidative and alkylating DNA damage) as well as possible synergic effects of studied natural antioxidants.

Recent international cooperation of the research team

Institute of Genetics and General Biology, The University of Salzburg, Salzburg,
Hellbrunnerstrasse 35, 5020 Austria;
Section for product Toxicology, The National Institute of Public Health, Folkehelsa, Geitmyrsveien 75, Oslo, Norway.

Proposer´s relevant publications related to the research subject

SLAMENOVA D., GABELOVA A., CHALUPA I., RUZEKOVA L., HORVATHOVA E., FARKASOVA T., BOZSAKYOVA E., STĚTINA R.: Detection of MNNG- induced DNA lesions in mammalian cells; Validation of comet assay against DNA unwinding technique, alkaline elution of DNA and chromosomal aberrations, Mutation Res. 83, 243-252 1997.
ROBICHOVA S., SLAMENOVA D.: Study of N-nitrosomorpholine-Induced DNA Strand Breaks in Caco-2 Cells by the Classical and Modified Comet Assay: Influence of Vitamins E and C. Nutrition and Cancer, 39(2), 267-272 2001.
SLAMENOVA D., HORVATHOVA E., KOSIKOVA B., RUZEKOVA L., LABAJ J.: Detection of lignin biopolymer- and vitamin E- stimulated reduction of DNA strand breaks in H2O2- and MNNG- treated mammalian cells by the comet assay, Nutr. Cancer 33 , 88-94, 1999