Biomarkers Of The Cell Genome Damage In Ecogenetic Research
Principal Investigator: Verica Garaj Vrhovac
(The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006))
Principal investigator: Verica Garaj-Vrhovac,
Ph.D.
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 on chemo-
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.