Projects / Programmes
Ecotoxicology, toxicological genomics and carcinogenesis
January 1, 2004
- December 31, 2008
| 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 |
|
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B003 |
Biomedical sciences |
Ecology |
| B260 |
Biomedical sciences |
Hydrobiology, marine biology, aquatic ecology, limnology |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
| B470 |
Biomedical sciences |
Physiology |
| B700 |
Biomedical sciences |
Environmental health |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
| B420 |
Biomedical sciences |
Nutrition |
apoptosis, angiogenesis, carcinogensis, cytoskeleton, DNA damage and repair mechanisms, ecotoxicology, genetic toxicology, invasion, metastasis, microcystins, health ecology, oncology, proteolytic enzymes and inhibitors, toxicologic genomics
Researchers (22)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0105 |
National Institute of Biology |
Ljubljana |
5055784 |
0 |
Abstract
Today, we recognise that the rapidly growing incidence of cancer is increasing, mostly due to the increasingly polluted environment, The research programme on carcinogenesis is therefore comprises the investigation on disrupted balance in water environment, the effect of biological peptides on cells and nuclei of higher organisms. Initiation and firther processes of cancer progression. In eutrophic water environment, the abundant proliferation of cyanobacteria causes a mass production of cyclic peptides and their release in the environment. The microcystins together with a number of other biologically active peptides are able to harm cells of higher organisms. These substances act as genotoxic agents, affecting the cellular biochemical pathways, which can under certain conditions lead to cancer initiation. The investigations of the above phenomena are carried out in three directions, as follows:
The investigations are carried out in three directions:
A) The research of surface waters comprise studies of general water eutrophication, with the emphasis on cyanobacterial proliferation (blooms) and their effects on biodiversity. It is focused on the research of the effects on photosynthetic apparatus of various phytoplankton organisms in vitro and on studies of the involvement of microcystins on the domination of the toxic bacteria. We are identifying which of the phytoplankton species are most sensitive to the presence of cyanobacterial cyclic peptides and therefore excluded form the water body.
B) The research on the effects of biological toxins, such as microcystins and other toxins from the environment, on gene integrity, particularly on the balance between DNA damage and repair, and possible mutagenic activity of these toxins, which may lead to cancer initiation and promotion. We investigate the acute and long term toxic effects on mammalian (CHO) cells and human liver cells (HepG2). We also study the mechanisms of genotoxic activity of some food borne carcinogens such as heterocyclic amines and specific environmental pollutant, such as cadmium and their combinations. Similarly, we also study the mechanisms of action of potential plant anti-mutagens (i.e. acitve ingredients of hops).
C) In the carcinogenesis part, we investigate the progression of transformed cells to the cancer cells, with the emphasis on the studies of apoptosis, invasion and metastasis. Investigating the alterations of cell signalling, we mainly focus of proteolysis signalling, in particular the system of cysteine proteases and their inhibitors, as their balance is disrupted in the process of cancer progression, either in the tumour cells or/and in their microenvironment. We investigate the in vitro cell systems of breast carcinoma and glioma, the latter a also includes clinical studies.
The knowledge and understanding of the above described phenomena (A) at cellular and molecular levels is important for improving the water environment, and for improving the detection systems and assessment of the effects of biological toxins at molecular level. The application of these researches includes the studies of and use of anti-mutagens from natural origin in cancer prevention (B). The knowledge of the mechanism of nuclear material damage and cell death may lead to the development of new targets and actions of drugs for cancer treatment (C). The understanding of altered proteolytic signalling has a potential for development of new diagnostic and prognostic parameters.
Significance for science
The advantage and the scientific originality of the programme lies in the unique interdisciplinary of the programme group what enables the link between the environment and development of neoplastic diseases. By the te research on cellular and molecular mechanisms, using novel methods of genetic and systems biology, we are discovering associations between natural environmental toxins (ecotoxins), dietray carcinogens (heterocyclic amines) and artificial pollutants (pesticides, heavy metals, etc.) with human genetic material, the damage of which is causing various diseases including cancer. We are developing new methods for carcinogen detection and we are looking for new targets and natural substances for prevention and supression of cancer . Today we know that cyclic cyanopeptides possess important biological activities and therefore we cannot anymore refer to them as non-toxic cyclic peptides. The discovery of their new biological activities on different organisms in the ecosystem will provide a more realistic basis for cyanobacterial bloom risk assessment. Our proposed new theory of endogenous triggers in bloom lysis offers the explanation of this dangerous event in cynobacterial blooming and the possibility of the bloom collapse prediction, what is important for human and environmental health protection. Cyclic peptides represent new tools in the study of natural processes both in organisms and in the environment and have potential application in medicine. The toxicogenomic research offer new knowledge on the molecular mechanisms of carcinogenicity of most common genotoxins and most important carcinogens and on the other hand of the anticarcinogenic activity of certain food constituents. The use of novel bioinformatics approaches and modern analysis of gene expressions will enable the identification of molecular targets of these effects. Due to increasing limitation of animal testing in toxicology, we are also developing new strategies and methods to screen large numbers of chemicals for potential carcinogenicity. We focus on studying those substancies (dietary carcinogens, pesticides, metals, natural toxins) that present the greatest likelihood of risk to human health and to the environment, and to new emerging contaminants (nanopartices, residues of pharamaceutical and cosmetic products in the environment). It is well known, that sublethal long term exposure to toxic and also non-toxic substances in our environment may lead to cancer. As carcinogenesis is a stepwise process, involving the activation of a set of peptidases (proteases), it is of utmost importance to better understand the network of proteases, their inhibitors and substrates, collectively known as the “cancerdegradome˝, in specific processes leading to cancer progression. Although protease inhibitors are good candidates as anticancer drugs, the poor outcome of recent clinical trials has clearly shown that too early application may do more harm than good. Therefore, a better fundamental understanding of the proteolytic complexity in tumours is essential and this programme has contributed to this knowledge. In addition, part of the programme was already aimed to a yet poorly explored area, e.g. proteolytic regulation in stem cells. The latter play an important role not only in carcinogenesis , but also in therapy of cancer by introducing normal stem cells. Therefore, good basic research on stem cell in cancer is absolutely needed for their application in clinical testing.
Significance for the country
Clear and unpolluted drinking water becomes one of the key issues globally and locally. The pollution of available water resources will be addressed in this programme by two aspects; first, the studies on the phenomenon of cyanobacterial blooms and the release of natural toxins upon their disintegration revealed how strong is their influence on the biodiversity and disruption of the natural balance in water bodies. The information about potentially dangerous substances in the environment will raise public awareness and lead to a more sustainable management with natural resources. This has not only high economic impact, but may also further effect climate changes globally. The second, practical approach is the development of a battery of toxicological assays for toxicity and genotoxicity testing of chemicals and products as well as for a more efficient water pollution monitoring, particularly with respect to introduction of various anthropogenic substances with sublethal, long term genotoxic effects. The presence of genotoxic contaminants in surface, ground and drinking waters is of special concern for human health. Our group is already conducting a number of applied projects on toxicogical properties of waters, which enables the recognition of the general quality conditions of water bodies in Slovenia, identification of sources of water pollution and classification of surface waters to quality classes. In the frame of this programme, we have already developed non invasive methods of tracing, which we proposed to trace directions of pollution of water resources and mixing of surface and ground waters. Thereby, we could introduce and follow the European Programmed of Chemical Safety (REACH) and European Water Directive in our country, with the goal to reach good water status until 2015. The results of our research will provide useful data base for toxicological water status, which is, together with chemical analyses, crucial to implement actions for improving and sustaining fresh water quality in Slovenia. Thirdly, due to increased environmental pollution, cancer incidence in increasing in Slovenia and. increased incidence of brain tumours among young generation is worrisome as patients with glioblastoma have a life expectancy of under a year in spite of novel treatment strategies. During this research Programme we have discovered novel sources of natural (cyanobacterial, hop plant) active substances and synthetic protease inhibitors, having anti-invasive and pro-apoptotic potential and found out that they can act synergistically with chemotherapeutics for glioblastoma. Here, we closely collaborate with the Department of Neurosurgery of the University Clinical Centre Ljubljana. Novel drug delivery vectors in GBM treatment are also stem cells, which are already used for treatment of various diseases. In Slovenia,we collaborate with the company Educell d.o.o. in applied projects and we initiated the establishment of the Centre for Stem Cells Research and Application in collaboration with Blood Transfusion Centre and all other institutions that are active in the field. Noteworthy, we are collaborating on all the above research with the relevant recognised international research institutions all over the world.
Most important scientific results
Final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
