Progetti di ricerca

Cadmium is a well recognized carcinogen, primarily released into the environment by anthropogenic activities (30,000 tons/year). In the effort to understand the early events responsible for cadmium carcinogenesis, we propose the use an in vitro biological system (the Cell Transformation… Leggi tutto Assay, CTA), that has been shown to closely model some key stages of the conversion of normal cells into malignant ones. Cadmium-triggered early responses in CTA will be analysed through microarray-based toxicogenomics. Protein expression of specific and non-specific targets of cadmium will be investigated consequently to transcripts analysis. The comparison of early events with those features in transformed cells (foci) will suggest the triggering mechanisms, and will provide hints on possible protective and/or preventive substances. Along with carcinogenesis, a role of cadmium in neurotoxicity and neurodegenerative diseases is emerging. For example, amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the voluntary motor nervous system. Genetic factors play a major role in the familial form, represented by 10% of cases. Whereas, in the remaining 90% sporadic cases a multifactorial origin is supposed, in which environmental factors may be involved. Particularly, the involvement of metal toxicity is proposed, based on epidemiologic data and on the increasing number of case reports of ALS-like syndromes associated to metal exposure. Studies of neurodegenerative diseases mainly rely on the use of animal models and on stem cells. Already ten years ago in a Nature Report the validity of neurodegenerative disease animal models was questioned, and direction towards the reduction of transgenic models is mandatory. In this direction, to investigate cadmium neurotoxic effects a human neuronal cell line will be used. The application of a toxicogenomic approach will evidence deregulated pathways in SH-SY5Y human neuronal cells exposed to cadmium to unravel neuronal specific and non-specific responses to the toxic metal. All the results from different techniques and approaches (toxicogenomics, specific markers expression, in silico and in vitro methods) will be integrated to better understand the carcinogenic and neurotoxic potential of cadmium.