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Projects / Programmes source: ARIS

Chemical Carcinogenesis: Mechanistic Insights

Research activity

Code Science Field Subfield
1.04.02  Natural sciences and mathematics  Chemistry  Structural chemistry 

Code Science Field
1.04  Natural Sciences  Chemical sciences 
Keywords
biomolecular simulations, free-energy calculations, aflatoxins, cytochromes P450, DNA polymerases, biochemical cooperativity, DNA catalysis, DNA adduct longevity, DNA replication fidelity, scavengers of chemical carcinogens, microwave effects
Evaluation (rules)
source: COBISS
Points
25,608.23
A''
4,859.6
A'
14,405.4
A1/2
19,790
CI10
41,225
CImax
3,392
h10
83
A1
80.92
A3
19.78
Data for the last 5 years (citations for the last 10 years) on June 21, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender, archive )
Database Linked records Citations Pure citations Average pure citations
WoS  1,457  49,197  43,556  29.89 
Scopus  1,474  55,015  49,101  33.31 
Researchers (40)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  53574  Sašo Bjelić  Chemical engineering  Junior researcher  2020 
2.  52081  Dragana Borjan  Chemical engineering  Junior researcher  2020 - 2022 
3.  25434  PhD Urban Bren  Chemistry  Head  2020 - 2024 
4.  53575  Matic Broz  Chemistry  Junior researcher  2020 - 2024 
5.  50420  PhD Tine Curk  Chemistry  Researcher  2020 - 2024 
6.  36818  PhD Helena Sabina Čelešnik  Biochemistry and molecular biology  Researcher  2021 - 2023 
7.  09892  PhD Metka Filipič  Biology  Retired researcher  2020 - 2024 
8.  28477  PhD Matjaž Finšgar  Chemistry  Researcher  2020 - 2024 
9.  08762  PhD Regina Fuchs-Godec  Chemistry  Researcher  2020 - 2021  32 
10.  50635  PhD Veronika Furlan  Chemistry  Researcher  2020 - 2024 
11.  37458  PhD Martin Gladović  Chemistry  Researcher  2020 
12.  36321  PhD Klara Hercog  Biology  Junior researcher  2020 
13.  34351  PhD Gregor Hostnik  Chemistry  Researcher  2020 - 2024 
14.  06734  PhD Dušanka Janežič  Computer intensive methods and applications  Researcher  2020 - 2024  63 
15.  32587  PhD Marko Jukič  Pharmacy  Researcher  2020 - 2024 
16.  02619  PhD Željko Knez  Chemical engineering  Researcher  2020 - 2024 
17.  38261  PhD Anja Kolarič  Pharmacy  Researcher  2022 - 2024 
18.  25435  PhD Janez Konc  Computer intensive methods and applications  Researcher  2020 - 2024 
19.  52671  Katarina Kores  Chemistry  Researcher  2020 - 2024 
20.  55088  Sebastjan Kralj  Biotechnology  Researcher  2021 
21.  15669  PhD Jurij Lah  Chemistry  Researcher  2020 - 2024 
22.  00534  PhD Maja Leitgeb  Chemical engineering  Researcher  2020 - 2024  118 
23.  37452  PhD Samo Lešnik  Pharmacy  Researcher  2022 - 2024 
24.  27882  PhD Miha Lukšič  Chemistry  Researcher  2020 - 2024 
25.  51984  PhD Bernarda Majc  Biology  Junior researcher  2020 - 2022 
26.  35511  PhD Tinkara Mastnak  Chemistry  Researcher  2020 - 2022 
27.  52556  PhD Snehashis Pal  Chemistry  Researcher  2023 - 2024 
28.  39608  Anja Petek    Technical associate  2020 
29.  16340  PhD Uroš Potočnik  Microbiology and immunology  Researcher  2020 - 2024 
30.  50950  PhD Martin Rozman  Chemistry  Researcher  2020 
31.  51845  PhD Matjaž Simončič  Chemistry  Junior researcher  2020 - 2022 
32.  39119  PhD Martina Štampar  Biology  Junior researcher  2020 
33.  32094  PhD Alja Štern  Control and care of the environment  Researcher  2020 - 2024 
34.  55319  Zala Štukovnik  Chemistry  Researcher  2022 - 2024 
35.  52708  Sara Štumpf  Chemistry  Researcher  2020 - 2024 
36.  52709  PhD Jelena Tošović  Chemistry  Researcher  2020 - 2024 
37.  53933  Armando Tratenšek  Pharmacy  Researcher  2020 
38.  02563  PhD Vojeslav Vlachy  Chemistry  Retired researcher  2020 - 2024  79 
39.  53449  Uroš Zavrtanik  Chemistry  Junior researcher  2020 - 2024 
40.  20767  PhD Bojana Žegura  Biology  Researcher  2020 - 2024 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0794  University of Maribor, Faculty of Chemistry and Chemical Engineering  Maribor  5089638012  493 
2.  0103  University of Ljubljana, Faculty of Chemistry and Chemical Technology  Ljubljana  1626990  1,129 
3.  0105  National Institute of Biology  Ljubljana  5055784  445 
4.  2790  University of Primorska, Faculty of mathematics, Natural Sciences and Information Technologies  Koper  1810014009  524 
Abstract
Chemical Carcinogenesis represents a complex multi-stage process that begins with the exposure to harmful chemicals and ends with the formation of neoplastic cells. The proposed research project will for the first time computationally address the entire process of early carcinogenesis. It will also include possible human interventions in the form of omnipresent microwave irradiation and dietary polyphenols. Research proposal concerns food safety with emphasis on chemical carcinogens that are present either in raw or in thermally processed foods and which after initial activation alkylate DNA, typically at the N7 atom of guanine. Important biochemical phenomena like DNA catalysis of the resulting genetic damage, biomolecular cooperativity, DNA adduct longevity or DNA polymerase mutational propensity were recently discovered and still lack an appropriate mechanistic understanding. A range of state-of-the-art computer simulation techniques in conjunction with free-energy calculations and dedicated thermodynamic cycles will be applied to elucidate their molecular basis. Because microwaves are reported to catalyze a variety of chemical reactions, we are concerned with microwave enhanced reactivity of chemical carcinogens, which has the potential to explain why microwaves were recently classified as potentially carcinogenic to humans by the World Health Organization. Therefore, reactions between chemical carcinogens and DNA will be modeled in the context of our newly proposed physical mechanism of microwave catalysis based on rotationally excited reactive species. Moreover, microwave irradiation is also reported to enhance protein folding and aggregation, events which are generally associated with several neurodegenerative disorders as well as with certain cancer types like amyloidoses. Molecular dynamics simulations in conjunction with home-developed Split Integration Symplectic Method (SISM), which is able to effectively decouple individual degrees of freedom of water molecules and to connect them with corresponding thermostats, will be applied to test the hypothesis that the microwaved aqueous solution through the rotationally hot water molecules represents a less polar and less protic medium thereby promoting the processes of aberrant protein folding and aggregation. Furthermore, reactions between chemical carcinogens and polyphenols – natural compounds abundant in fruits – will be studied using quantum-chemical approaches. The underlying concept is that, in order to prevent DNA damage, chemical carcinogen has to react faster with its polyphenolic scavenger than with DNA. Since activation free energy presents a direct measure of reactivity, the free-energy barrier for the reaction of chemical carcinogen with its scavenger has to be lower than for the competing DNA alkylation. Finally, our novel inverse molecular docking protocol will be applied to discern polyphenols which inhibit protein targets involved in oncogenic signaling cascades. The ultimate goal is to discover natural compounds or their mixtures with high antigenotoxic activities which, after subsequent optimization, could serve as food supplements contributing much towards the prevention of cancer. We will seek experimental verification of the calculated results from our long-term collaborators whenever possible in order to establish a validated computational platform offering clear advantages over the wet-lab experiments that are in the field of Chemical Carcinogenesis inevitably associated with high health and environmental hazards.
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