Projects / Programmes
Ecotoxicology, toxicogenomics and carcinogenesis
January 1, 2019
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 1.08.00 |
Natural sciences and mathematics |
Control and care of the environment |
|
| 1.03.00 |
Natural sciences and mathematics |
Biology |
|
| Code |
Science |
Field |
| B003 |
Biomedical sciences |
Ecology |
| Code |
Science |
Field |
| 1.05 |
Natural Sciences |
Earth and related Environmental sciences |
| 1.06 |
Natural Sciences |
Biological sciences |
Environmental protection, Aquatic ecosystems, Aquatic bio indicators, Bio assessment, Pollutants, Toxicogenomics, Genotoxicity, Endocrine disruptors, Cancer initiation, Biomarkers, Glioblastoma stem cells, Tumour microenvironment, Mesenchymal stem cells, Cancer stem cell niches, Irradiation.
Data for the last 5 years (citations for the last 10 years) on
April 19, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
549 |
21,152 |
18,893 |
34.41 |
| Scopus |
561 |
23,183 |
20,802 |
37.08 |
Researchers (27)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0105 |
National Institute of Biology |
Ljubljana |
5055784 |
13,256 |
Abstract
Environmental pollution represents a serious threat for the ecosystem and human health. The origin of pollution is both, man-made compounds released to the environment as well as natural compounds produced by various organisms. Despite growing evidence of the presence of diverse compounds in water, food and air to which we are exposed, there are still gaps in our understanding how these chemicals affect living organisms, preventing more exact risk assessment for environment and human health and particularly human cancer risk assessment. Therefore, the main aim of the Program is to explore the effects of anthropogenic and natural toxicants as well as irradiation on environment and human health and their role in cancer initiation and development.
Among the toxic environmental pollutants, genotoxic and endocrine-disrupting agents are of particular concern as they exert their adverse effects with a delay. In the environment, these pollutants occur at low concentrations at which toxic effects are not detected with standard ecotoxicological tests and the consequences of chronic exposure, which is typical for environmental exposure, cannot be predicted. Within this Programme, we will develop and apply novel approaches using the combination of classical toxicology tools with the latest developments based on “omics” technologies for comprehensive environmental and human hazard assessment of selected high priority contaminants and their trasformation substitutes.
Exposures to exogenous genotoxic substances, called “mutagens” (chemical and biological agents, radiation, and cancer therapeutics), as well as multiple endogenous restraints may result first in tissue field cancerization, the modern concept of cancer evolution. This results in tumor-initiating cell clones that further acquire stem cell-like characteristics over time and develop into malignant tumours. The abberant tumour microenvironment may create stem cell niches that protect these cancer stem cells, enabling tumour growth on the one hand, and on the other prevent their elimination by therapy. This dynamic aspect of cancer development will be addressed here in the most aggressive brain tumour, glioblastoma (GBM) by investigating GBM stem cells, as the key target of modern cancer therapy. Besides, the tumour microenvironment will be investigated with respect to GBM stem cell niches, composed of various types of stromal cells. We aim to interfere with their mutual cross-talk to disrupt the protective niches and thereby reduce GBM stem cells resistance. In all experimental approaches the inter-cellular heterogeneity of patient-derived GBM cells, comprised of classical, neural, proneural and mesenchymal cell subtypes, being more or less differentiated, as are the cancer stem cells, will be considered with respect to their various and specific resistance to therapeutics, aiming to develop personalized treatment approach. Novel, state of the art methodological approaches will be applied to perform this research.
Significance for science
The key scientific premise of this Programme relates to direct and indirect anthropogenic pollution and environmental genotoxic compounds that in the long term affect ecosystem and quality of human health. For many tyes of diseases we can only speculate with respect to environmental causes bur cancer initiation is a direct consequence of damaged genetic material by numerous mutagens in ofthe air, water, soil, and food. The protection against and prevention of these effects from emerging environmental pollutants can only be achieved by creative scientific solutions, innovative approaches in problem solving, resulting in their application either to eliminate causes, or preve their harmful effects
With respect to the water environment, the assessment of the ecological status is facing serious challenges, due to the limitationsof the traditional time-consuming classical identification of biological species, e.g. algae (phytoplankton and phytobenthos). Therefore, sate of the art molecular tools are now complementing traditional monitoring approaches, allowing faster and more precise bioindicator identification on the basis of environmental DNA and better ecological satus assemeesment of water bodies. We are participating in the international networking projects (e.g. COST Actions) aiming to synchronise these state of the art approaches.
Genetic toxicology research enables understanding of molecular mechanisms of several anthropogenic and natural pollutants, such as pharmaceuticals and their transformation products, bisphenols, nanoparticles, PAHs, industrial waste waters, hormone disruptors, either as individual compounds or as complex mixtures. We will study the adverse effects in advanced animal and human cell systems that are revealing new targets, and so far missing data for predicting delayed effects of chronic exposure to low concentrations of potentially genotoxic and endocrine disrupting compounds. For this purpose, we are applying innovative holistic approach, combining traditional toxicological tests with the latest “omics” technologies and bioinformatics to identify novel biomarkers of the mechanisms of action that reflect complex underlying processes. This is important in the field of experimental and research-based regulatory toxicology, as there is an urgent need to develop new strategies and methods to screen and evaluate large numbers of chemicals for their potential adverse effects. Therefore, this programme has the potential to provide novel diagnostic tools for predicting endocrine disrupting and genotoxic effects of such pollutants. The results will contribute to improved risk assessment of natural ecosystems and human health by providing data on predictive environmental concentrations and toxicological properties of a particular compound, as well as the key data on toxicological parameters that are required for risk assessment. These approaches will enable prioritisation of the most efficient entities and the most relevant end-points to define the health risk. A particular scientific challenge is also to develop novel cell lines by stem cells differentiation as well as 3D-cell systems replacing classical liver-cell based cell lines to be used in genotoxicity testing. In addition, zebrafish embryo assay is effectively replacing animal assays, leading to better understanding and interpretation of toxicological results.
The highest risk for health in this respect, as the consequences of genotoxic and endocrine disrupting compounds, is undoubtedly the initiation of cancer. A large body of data suggest that many types of cancer could be prevented by avoiding harmful substances in water, food, and feed. Exposures to mutagens (chemical and biological agents, radiation, and even cancer therapeutics), exert pressure on tissue clonal architectures and dynamics, resulting in the so called tissue field cancerization leading to cancer evolution. The resulting tumor-initiating clones can further
Significance for the country
Environmental pollution by human-made and natural and toxic compounds is one of the major problems in ecotoxicology. These pollutants are present in air, soil, food, feed, and water and act via a plethora of possible direct and indirect interactions affecting environment and human health. This Programme aims at studying effects of anthropogenic and natural toxins in the environment and their potential to initiate cancer. Protection of endangered environments, as well as prevention and treatment of cancer, on the basis of scientific evidence of harmful activities of these compounds are the major benefits of the proposed research for science and society.
In the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH)
legislation the main contribution of the research results of this Programme will be the development of alternative methods for the assessment of hazards of different (chemical) substances through identification, evaluation, and confirmation of predictive potential of in vitro test systems for long term in vivo effects based on early biological and molecular markers. We are developing sophisticated targeted 3D liver-cell systems for more relevant in vitro genotoxicity testing. In parallel, because animal protection rights consequently enforce avoidance of higher animal species, we used instead zebrafish embryos. The major contribution to the environmental protection for society as a whole, is our OECD accredited Good Laboratory Practice (GLP) laboratory where analyses of compounds safety are already carried out for public institutions and private companies.
Protection of water resources is a major concern in EU, which is covered by Water Framework Directive (2000/60/EC). At present, the assessment of the ecological status of waters is facing new challenges by implementation of novel analytical tools, comprised of molecular biology based-assays for faster and more effective evaluation to support the actions by the governmental bodies responsible for water management. Within this Programme, we aim to provide improved detection of potentially hazardous toxic cyanobacteria and other pollutants in aquatic environments that have adverse effects on animals and humans. Novel molecular tools for early detection of toxic cyanobacteria can be implemented in water management for irrigation systems, drinking water, etc. From economic perspectives, early detection of hazardous pollutants is relevant also in touristic areas, e.g. Alpine lakes, rivers and the sea. Our role and aim in these activities is also to bridge the gap between academia and governmental entities responsible for water management, to increase the support for research-based solutions in water protection. Within this programme, we will include the research on marine organisms, such as jelly fish, not only as a threat to the natural environment, but also from an environmental biotechnology aspect, being a source of natural substances to be used in sea-water-cleaning devices.
In developed countries, cancer is among the most relevant socio-economic problems and health priority. Cancer research is highly financially supported, as it is still considered to be an incurable disease and represents a serious socio-economic problem. This affects not only individuals, but also their families and society as a whole, being a burden to health-care systems and state economies in general. However, in spite of increasing incidences, significant decreased in mortality of various types of cancers is already evident, mostly due to early biomarkers-based non-invasive diagnostic tools and screening programmes. Furthermore, growing understanding of cancer initiation, and cancer progression improves cancer treatment and expands diseases-free intervals.
This is the subject of this programme, where we are for more than a decade investigating glioblastoma (GBM), the most aggressive type of brain tumours. GBM is classified as rare disease, but i
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
