022-0222148-2125 Mutagens and antimutagens in ecogenetic research

Principal Investigator: Verica Garaj Vrhovac
[The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)]

SUMMARY
Primary DNA damage and spontaneous mutations that occur in the cell genome as a consequence of mutagen and carcinogen action, are considered to be biomarkers of genotoxic stress. They represent an additional genetic burden, increase a risk and are one of the stages in neoplastic disease development.

Genetic susceptibility for neoplastic disease development always includes certain genome instability. Structural chromosomal rearrangements are considered to be one of the crucial moments in the cancer development. In order to evaluate the risk, cytogenetic assays on surrogate cells and tissues are used as biomarkers of genetic damage.

The aims of the project proposed will focus on the application and improvement of sensitive molecular-biological technics for the detection of genome damage caused by mutagens and carcinogens in vitro and in vivo. New technics in the early neoplastic-disease-biomarkers detection will be developed. On animal and human models, mechanisms of biomarker induction and their reliability as genotoxic stress indicator will be studied.

Biomarker research will point out internal mutagen doses which make the detection of interindividual differences in DNA repair mechanism possible, and are involved in increased susceptibility and cancer development risk. Highly susceptible subjects in the population will be studied. Potential genetic markers and new technology for rapid evaluation of cell response onchemo– and radio therapy will be studied. The value of biomarkers that could be used in preclinic and clinic researches will be estimated. Sinergistic effects of mutagens and antimutagens that have impact on biomarkers will be compared.