Projects / Programmes
Molekularni mehanizmi sinergističnih in antagonističnih toksičnih učinkov heterocikličnih aminov v kombinaciji z bioaktivnimi prehranskimi onesnažili in naravnimi sestavinmi (Slovene)
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| 4.04 |
Agricultural and Veterinary Sciences |
Agricultural biotechnology |
Researchers (15)
Organisations (2)
Significance for science
Carcinogenic heterocyclic aromatic amines (HCA) are readily formed in grilled meat and when eating meat we cannot avoid exposure to these carcinogens. The aim of this interdisciplinary project was to elucidate the molecular mechanisms of the activity HCAs at the conditions of actual exposure that typically involves exposure to complex mixtures of different HCAs and concurrent exposure to other bioactive compounds that may increase or suppress the adverse effects of HCAs. The results showed that in HepG2 cells HCAs induce DNA damage, while at the molecular level they modulate expression of genes encoding for metabolic enzymes, DNA damage responsive genes and apoptotic gens. Quantification of the molecular responses showed that mixtures of HCAs as well as the extracts of grilled meat (prepared under controlled conditions and with defined content and composition of HAAs) act synergistically on the expression of metabolic genes as well as DNA damage responsive genes. This is important new finding, which indicates that risk assessment for human health based on the effects of single HCA may underestimate the risk. New models should be developed that will take synergism into account. Based on the pattern of the differential expression of apoptotic gens we found that HCA may suppress intrinsic apoptotic pathway. This indicates that inhibition of apoptosis may be a mechanism that contributes to carcinogenic activity of HCAs, which remains to be explored.
Several previous studies, including ours, showed that xanthohumol (XN), the prenylated flavonoid of hops, efficiently suppress genotoxic activity of indirect acting genotoxins, to which belong also HCAs. The analysis of the changes in gene expression of the enzymes involved in the metabolism of HCAs performed after concurrent exposure to XN and HCA showed that the mechanism of XN mediated protection against the genotoxicity of HCAs is activation of detoxification by UDP-glucuronyltrasferase. In collaboration with the colleagues form the Medical University in Vienna we confirmed protective effect of XN against carcinogenicity of HAA also in rats. These results are now opening the way to further research of chemopreventive properties of XN in humans that may include also volunteers.
Significance for the country
The results of this project may contribute to the improvement of human health, which will have also indirect benefits for Slovenian society and economy. It is well documented that the diet plays a crucial role in the aetiology of cancer in humans. Of particular interest is the role of heterocyclic aromatic amines consumed through grilled meat, which is common in Slovenian population. There is strong epidemiological evidence that meat consumption is associated with certain cancers, therefore the new knowledge of the complex mechanisms of their activity will enable more adequate, scientific based advice to customers regarding protection against the adverse consequences of consumption of meat. Ultimately, improvement in the human diet can reduce the risk of cancer in Slovenian and European populations and contribute to improvements in overall health. This will certainly assist in controlling costs of hospitals and follow-up treatments.
The results of the studies of the chemopreventive activities of xanthoumol are at the level that allows for the beginning of the development of food supplements. We will disseminate our results to relevant traders and try to find the ones that will be interested for the development of products with high added value.
Most important scientific results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
