Speciation, bioavailability and antigenotoxicity of Selenium species present in Selenium enriched natural products.
Nowadays, it is well known that Selenium plays an important role as chemopreventive agent in carcinogenesis and that is the reason why it has been widely used in nutritional supplements. This Se antimutagenic and/or anticarcinogenic activity is related not only with the total Se ingested but also with the chemical form. Therefore, there is an increasing demand on the development of adequate analytical methodologies able to perform separation and determination (speciation) of the different Se species present in Se enriched natural products (yeast, garlic, onion, etc). These products have had some use as therapeutic and/or nutritional agents. The development of such methodologies constitutes the first objective of the present Project. On the other hand, one of the mechanistic approaches suggested in order to explain Se chemopreventive effects is related to the inhibition of DNA-adducts formation. Mutagenic effects have been described as formation of DNA adducts with genotoxic agents such as environmental contaminants (e.g. PAHs) or therapeutic drugs (e.g. cisplatin). The formation of these adducts seems to be a crucial step on the development of malignant tumors since they can produce mutations on the DNA. Such mutations can further produce the transformation of normal cells into carcinogenic ones. Thus, the second objective of the present project will be the development of analytical methods to determine ADN adducts with dimethylbenzo(a)antracene (as model PAH) and cisplatin. Finally, the developed methodologies will be used in order to study the effect of Se species in natural products in the DNA adducts formation. These studies will be carried out by in vitro and in vivo experiments using, in the last case, Drosofila Melanogaster as model organism.