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Projects / Programmes source: ARIS

Mechanisms of genotoxic activity of chemicals and cellular response to DNA damage

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Research activity

Code Science Field Subfield
1.03.00  Natural sciences and mathematics  Biology   

Code Science Field
B220  Biomedical sciences  Genetics, cytogenetics 
Keywords
genotoxicity, antigenotoxicity, reactive oxygen species, metabolism, HepG2 cells, heavy metals, heterocyclic amines, comet assay, micronuclei, test methods, chemoprevention
Evaluation (rules)
source: COBISS
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Researchers (9)
no. Code Name and surname Research area Role Period No. of publications
1.  19157  PhD Tanja Fatur  Public health (occupational safety)  Researcher  2004  310 
2.  09892  PhD Metka Filipič  Biology  Head  2004 - 2007  584 
3.  25524  PhD Irena Hreljac  Biochemistry and molecular biology  Junior researcher  2006 - 2007  48 
4.  07744  PhD Gorazd Kosi  Biology  Researcher  2005 - 2007  359 
5.  07802  PhD Tamara Lah Turnšek  Biology  Researcher  2004 - 2007  1,012 
6.  23609  PhD Janja Plazar  Educational studies  Junior researcher  2004 - 2007  215 
7.  07736  PhD Bojan Sedmak  Biochemistry and molecular biology  Researcher  2004 - 2007  232 
8.  16193  Nataša Sever  Pharmacy  Researcher  2004 - 2007  30 
9.  20767  PhD Bojana Žegura  Biology  Researcher  2004 - 2007  315 
Organisations (1)
no. Code Research organisation City Registration number No. of publications
1.  0105  National Institute of Biology  Ljubljana  5055784  13,101 
Abstract
According to epidemiological studies diet plays major role in the ethiology of human cancer. It is convincible that consumption of contaminated foods which contain pesticides, mycotoxins, PCBs or heavy metals may enhance the carcinogenic risks of other food derived DNA reactive carcinogens. On the other hand there is also abundant evidence that the genotoxic and carcinogenic effects of food specific toxins are reduced by various plant constituents. However the overall experimental evidence for such synergistic and antagonistic effects is scarce due to the lack of appropriate testing methods. The main problem using in vitro test procedures to study complex mechanisms of putative synergistic and antagonistic effects of genotoxic chemicals is that conventional indicator cells require the addition of exogenous liver enzyme homogenates to activate procarcinogens. In the proposed project the mechanisms of genotoxic activity of chemicals will be studied with human Hep G2 cells which posses phase I and phase II enzymes such as CYP1A1, CYP1A2, CYP2E1 and glutathione-S-transferase in an inducible form and have better predictive value for the identification of genotoxic chemicals and their biological interactions. We will explore the mechanisms of induction of DNA damage and repair and the blological consequences. The role of specific enzymes in mutagenesis will be determined; induction/inactivation of metabolic and antioxidative enzymes as well as the role of reactive oxygen species in genotoxic effects. The main outcome s of the proposed studies will be: increase our knowledge for the mutagenic, co- and anti-mutagenic potential of certain important environmental contaminants and human food constituents, whivh will be used fro risk assessment and can ultimately be applied to improve human health. On the basis of the outcomes of these studies, attempts will be made to establish an in vitro assay model with the use of human derived hepatoma cell lines for studying complex chemical interactions, as an alternative to use of vertebrate animals.
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