Shedding light on cancer development Cancer is unambiguously one of the most formidable diseases taking variable forms, which requires commitment of research activities from various disciplines. With many recent advances, genetics constitutes a very promising field for bringing innovative prospects to cancers early prognosis and treatment. This EC funded project examined extensively the molecular mechanisms by which ionising radiation - an important cancer cause - induces cancer and genetic disorders. Health © Photodisc Exposure to ionising radiation constitutes a high risk for cancer development because the relevant energy is sufficient to cause chromosomal changes. However, there is a large variation in responses to radiation among human population depending largely on gene and gene products that influence radiosensitivity. Other important issues involve the function of these gene products from molecules to total organisms and the effects of these deficient genes on cells, animals and humans. The projects' key findings cover all major aspects of deoxyribonucleic acid (DNA) repair in cells that varies according to organ, organism, chromosomal structure and nuclear organisation. Among DNA repair pathways, the complex process of nucleotide excision repair was shown to be the predominant one. Isolation defected human repair genes from patients with cancer prone diseases (xeroderma pigmentosum) and rodent experiments allowed the study of the relation between repair functions and tumour development. Aiming to develop suitable biomonitoring technology, the sensitivity of different biological endpoints, such as chromosomal aberrations was assessed in human blood cells exposed to chemicals and ionising radiation. Additionally, using appropriate molecular cytogenetic techniques to subjects exposed to ionizing radiation, it was possible to make estimations of absorbed radiation dose under different exposure conditions (acute versus chronic). In daily life, humans encounter at least a million different electrophiles at different exposure levels whose interactions with genetic material are difficult to assess. All these agents affect DNA in cells that makes these agents potential carcinogens and radiation protection extremely difficult. Towards this need, new models currently under developement may be used for risk assessments of potentially environmental and occupational genotoxic agents. For this reason collaboration is sought with groups working on the risk assessment of mutagens and carcinogens.
