Determination of genotoxicity is an important element in the safety assessment of various substances, with the purpose of preventing a number of chemicals from affecting human health. Genotoxicity testing is required for all classes of chemicals, drugs and biological agents, which can lead to a wide range of diseases, cancer included. In the last decades, there has been an ongoing shift towards developing new effective testing methods, since a single test is not sufficient for the detection of all relevant genotoxic aspects; consequently, a variety of complementary testing techniques and methodologies have to be used. In addition, increasing emphasis is given to alternative in vitro models, which focus on the genotoxic effects of chemicals and environmental contaminants, thereby contributing to the reduction of animals used in preclinical testing. In the PhD thesis an approach for testing the genotoxic activity of chemicals was developed on a hepatocellular in vitro 3D cell model (spheroid) developed from a human hepatocellular carcinoma (HepG2 and HepG2/C3A) cell line by the forced floating method and cultured in a dynamic bioreactor (CelVivo BAM/bioreactor) system. The results showed that newly developed 3D cell models better illustrate in vivo conditions than traditional monolayer cell cultures, since they have improved cell-matrix and cell-cell interactions, as well as preserved in vivo cell phenotypes. Moreover, the thesis showed decreased proliferation over the cultivation period and a higher expression of liver-specific functions and genes encoding phase I and II metabolic enzymes in 3D models compared to 2D models. The novel hepatocellular in vitro 3D models cultured under static and dynamic conditions were used for the assessment of cytotoxicity and genotoxicity of xenobiotic compounds. The 3D cell models express genes related to metabolism and characteristic of hepatic cells to a higher extent than 2D models, showing a higher sensitivity to the detection of indirect-acting genotoxic compounds. The results of the PhD thesis were published in four highly ranked international Journals.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 49967107Prof. Tamara Lah Turnšek received in 2020 the Zois National Lifetime Achievement Award. In her scientific work, she strived for the integrity of her scientific work, which aimed to deepen and multifaceted view of the questions she posed and published in the number of scientific publications. Since her initial extraordinary discovery in biochemistry, a new proteolytic enzyme called cathepsin S she increasingly shifted to biomedical research - from inflammatory processes to cancer. Today, she focuses on understanding the malignancy of brain tumors. From the very beginning, she has successfully connected with clinical departments and laboratories, at home with the Oncology Institute and cancer centers in Europe, the USA and Brazil, thus enriching interdisciplinary biomedical and translational research. Through her international collaboration, she has made a significant contribution to academic exchanges and the circulation of “young brains”. The award-winning works also include efforts to raise the profile of science in society and politics, especially life sciences through a number of years of running the National Institute of Biology. Also efforts to equitably identify and promote the work of women in academia.
E.01 National awards
This fluorometric method is useful in many areas of research to detect and monitor aggregated microparticles, such as microorganisms, and organic as well as inorganic microparticles in suspension, that are capable of absorbing laser light radiation of specific wavelengths. The resulting emission of energy is assessed by simultaneous techniques of sensing their quantity and basic properties, such as size, shape, physiological properties… in the liquid or gaseous phase. The method is also useful for the effective detection of potentially toxic cyanobacteria and other pollutants in the aquatic environment and for the early on-line detection and differentiation of cyanobacteria from other phytoplankton in water, to prevent the spread of this dangerous phenomenon. The essence of our invention is in understanding the role of "noise" in pulse amplitude modulation of the obtained signal, which arises from the inhomogeneous space of feedback perception. From the superimposed signals we get all the additional information about the size, shape of the particles and the physiological state when the cells pass through the optimal point of detection. Because the process itself is dynamic, we get a series of different shots of the crowd. This information is manifested in constructive interference with a basic signal representing the total number of particles.
F.32 International patent
COBISS.SI-ID: 3783759Members of the P1-0245 program group are members of several editorial boards of international and national journals and editors as well: 1. Food and chemical toxicology. Filipič, Metka (član uredniškega odbora 2015-). Amsterdam [etc.]: Elsevier. ISSN 0278-6915. [COBISS.SI-ID 1218325] 2. Frontiers in marine science. Rotter, Ana (gostujoči urednik 2019, 2021, področni urednik 2020). Lausanne: Frontiers Media S.A., 2014-. ISSN 2296-7745. http://www.frontiersin.org/Marine_Science/archive. [COBISS.SI-ID 523094809] 3. ISRN Toxicology (Print). Filipič, Metka (član uredniškega odbora 2011-). Cairo: Hindawi Publishing Corporation. ISSN 2090-6188. [COBISS.SI-ID 2398543] 4. Journal of Environmental Sciences(China). Sedmak, Bojan (član uredniškega odbora 2013-). Amsterdam: Elsevier. ISSN 1001-0742. [COBISS.SI-ID 512542489] 5. Marine drugs. Rotter, Ana (urednik 2020). Basel: MDPI, 2003-. ISSN 1660-3397. http://www.mdpi.org/marinedrugs/. [COBISS.SI-ID 23578841] 6. Mutation research, Genetic toxicology and environmental mutagenesis. Žegura, Bojana (član uredniškega odbora 2016-). Amsterdam; Lausanne; New York; Oxford; Shannon; Tokyo: Elsevier. ISSN 1383-5718. [COBISS.SI-ID 1239829] 7. Mutation research, Reviews in mutation research. Filipič, Metka (član uredniškega odbora 2014-). Amsterdam; Lausanne; New York; Oxford; Shannon; Tokyo: Elsevier. ISSN 1383-5742. [COBISS.SI-ID 1240341] 8. Pathology oncology research. Lah Turnšek, Tamara (član uredniškega odbora 1997-). Budapest: Tud. Kiadó. ISSN 1219-4956. [COBISS.SI-ID 21115] 9. Poročilo o delu v letu .... Lah Turnšek, Tamara (član uredniškega odbora 1995-). [Tiskana izd.]. Ljubljana: Nacionalni inštitut za biologijo, [199-]-. ISSN 1408-3299. [COBISS.SI-ID 68115968] 10. Radiology and oncology. Filipič, Metka (član uredniškega odbora 2007-), Lah Turnšek, Tamara (član uredniškega odbora 2007-). [Print ed.]. Ljubljana: Slovenian Medical Society - Section of Radiology; [Zagreb]: Croatian Medical Association - Croatian Society of Radiology, 1992-. ISSN 1318-2099. http://www.degruyter.com/view/j/raon, https://www.radioloncol.com/index.php/ro, http://www.dlib.si/details/URN:NBN:SI:spr-FNIFVE9S. [COBISS.SI-ID 32649472] 11. Spatula : glasilo Študentske sekcije Slovenskega farmacevtskega društva. Breznik, Barbara (član uredniškega odbora 2010-). Ljubljana: Študentska sekcija Slovenskega farmacevtskega društva, 1997-. ISSN 1408-7650. [COBISS.SI-ID 79482624] kategorija: SU (S) točke: 10 12. Toxins : Elektronski vir. Žegura, Bojana (gostujoči urednik 2020-2021), Štern, Alja (gostujoči urednik 2020-2021). Basel: MDPI, 2009-. ISSN 2072-6651. [COBISS.SI-ID 517594649] 13. HEATH, Ester (urednik), ISIDORI, Marina (urednik), KOSJEK, Tina (urednik), FILIPIČ, Metka (urednik). Fate and effects of anticancer drugs in the environment. Cham: Springer, cop. 2020. XVI, 469 str., ilustr, graf. prikazi, tabele. ISBN 978-3-030-21047-2. [COBISS.SI-ID 304610560] 14. HEATH, Ester (urednik), ISIDORI, Marina (urednik), KOSJEK, Tina (urednik), FILIPIČ, Metka (urednik). Fate and effects of anticancerdrugs in the environment. Cham: Springer, 2020. XVI, 469 str., ilustr. ISBN 978-3-030-21047-2. ISBN 978-3-030-21048-9. https://link.springer.com/content/pdf/10.1007%2F978-3-030-21048-9.pdf. [COBISS.SI-ID 33111847]
C.06 Editorial board membership
COBISS.SI-ID: 1240341In the PhD thesis, two groups of pollutants originating from distinct sources were selected and their cytotoxic and genotoxic potential was assessed – cyanotoxins as naturally produced and bisphenols as anthropogenic pollutants. The dissettaion provided the first data on the genotoxicity of cyanotoxins L-BMAA and microginins. The comparison of genotoxic activity of bisphenol A and its most common analogues, bisphenols (BPs) S, F, and AF, revealed that BPAF has the highest genotoxic potential, despite the presumption that the analogues are safer than BPA itself. The transcriptomic analyses demonstrated that BPA and BPAF, as well as their combinations with other bisphenols, induced changes in gene expression also at low, for human exposure relevant concentrations. Combined exposure to bisphenols and cyanotoxin CYN confirmed the predominant DNA damaging effect of CYN, while transcriptomic analyses indicated additive or synergistic interactive effects in the CYN/BPs mixtures on the expression of several tested genes. In this study, a novel 3D in vitro HepG2 model, which has been recently developed, was applied for assessing the cytotoxicity and genotoxicity of CYN. CYN affected the growth of spheroids and induced cell cycle arrest and deregulated expression of genes involved in phase I and phase II metabolism, DNA damage response, cell proliferation and apoptosis. The results of the thesis provided the missing toxicological data of emerging pollutants - cyanotoxins and bisphenols, and contributed to better understanding of chemical interactions in the co-exposure. It was again confirmed that the concentration addition concept in mixture risk assessment is unjustified, since the experimental data indicate more complex interactions. Moreover, we emphasise the importance of considering the co-exposure to chemicals of distinct sources and functions, which is often neglected in risk assessment. The results of the PhD thesis were published in six highly ranked international Journals.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 32993795