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.

022-0222148-2135 Exposure to Metals and their Effects in Pregnancy and Postnatal Period

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Martina Piasek

SUMMARY
Toxic metals (such as lead, cadmium, mercury or arsenic) are ubiquitous environmental pollutants that occur in the ecosystem naturally or through human activity. Ill effects are related to metal overload due to external exposure or genetic factors (disturbed copper or iron metabolism), and to the deficiency or imbalance of essential metals and metalloids in the body (iron, copper, zinc, calcium, selenium). Women and children are vulnerable groups for ill effects of metals due to specific physiological features that can result in increased metal accumulation during childbearing age, gestation, lactation, and during child growth and development.

The aim of this project is an integrated assessment of exposure, biological effects, and interactions of toxic (cadmium, mercury, lead) and essential elements (iron, zinc, copper, selenium) during pregnancy/prenatal period and postnatal development. Sources of exposure will be evaluated by analysing metal content in food, soil, and selected tissues of wild animals, and using epidemiological variables in women. Metal concentrations in human placentas, in maternal and umbilical cord blood, and in organs and tissues of experimental animals exposed to toxic metal (cadmium or mercury) will serve as biomarkers of internal exposure. The effects of metal exposure will be assessed through steroid hormone concentrations in human and animal placental tissue. In experimental animals, we will also evaluate the methods for decreasing metal retention, such as supplementation with mineral (e.g. essential element selenium), vitamin (e.g. vitamin C) and/or chelation treatment (by deferoxamine, D-penicillamine, succimer, unithiol, deferiprone, or Prussian blue). The efficacy of these treatments in alleviating metal toxicity will be assessed through indicators of metal-induced oxidative stress. The proposed research will provide a new insight into the reproductive and perinatal toxicology of metals, into their toxicokinetics, and into the antidotal therapy in the young. Possibilities of research application are in public health measures, which include detection and prevention of metal exposure in vulnerable population groups, women in childbearing age and infants, as well as procedures for reduction of toxic metal body retention in postnatal period.

Dementia: An Electrophysiological and Genetic Study

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal investigator: Rajka Liščić

Duration: 1 July 2002-2005

SUMMARY
Dementia is a neurochemical disorder characterised by a decreased level of acetylcholine (Fassbender, 2001). One of the most common dementias is the Alzheimer’s disease (AD). In patients with AD as well as the fronto-temporal dementia (FTD) decreased level of acetylcholine results in a global cognitive impairment (Sorbi, 2000).

Various neuropsychological tests are used for diagnosis of dementia e.g. Stroop task (Spieler, 1996). As depression in AD may interfere with neurophysiological testing (Nacmias, 2001), event-related potentials (ERPs) have been proposed as a more objective neurophysiological tool of assessing cognitive processes (Pirtošek 2001). The ERP method, used in most studies, is the oddball paradigm (Liščić, 2001). Molecular analysis (tau, APP, presenilin gene) will enable a more accurate diagnosis.

The aim of our study is to compare a diagnostic value of three following methods in various patients with dementia:

  1. A bedside neurophychological testing (Mini-mental test),
  2. Auditory oddball ERP task (the P300 wave),
  3. ERP modification of the Stroop test.

We expect to clarify some pathophysiological mechanisms in various sorts of dementia, particulary the role of tau, APP and presenilin genes and to introduce new electrophysiological methods in the diagnosis of the disease. It is expected that by using more specific electrophysiological paradigm (the Stroop task) we will more successfully set apart fronto-temporal dementia from AD, than by the classical P300 paradigm.

It will have a significance for basic science (mechanism of the disorder) as well as for clinical application (specific, sensitive and cheap method in the diagnosis of cognitive disorders).

Occupational Stressors and Worker’s Health

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal Investigator: Milica Gomzi

SUMMARY
Due to changing of work patterns and work organisation the requirements of the job do not match the worker’s capabilities. Workers in jobs with high psychological demands combined with low work control most frequently show symptoms of stress. The objectives of this investigation are to determine 1. job characteristics known to produce stress reactions; 2. the frequency of early health disorders, psychological strain and behavioural changes; 3. the interacting factors, including psychological status, job task related features and ergonomic conditions; 4. potential relationship between long-term exposure to occupational stresses and the occurrence of some chronic medical conditions. Multidisciplinary approach and epidemiological methodology are applied: standardised questionnaires and diagnostic tests, medical examinations, ergonomic analysis of equipment, job tasks analysis, standardised interview, psychiatric examination and personality tests, descriptive and multivariate statistical analysis. The relationship of job stressors, life style, health, behavioural and personality characteristics are examined. Prospectively, the change of the level of perceived stress and of the characteristics of occupational stressors will be assessed two-years after introduction of intervention measures. The presence of comorbid conditions including diabetes, hypertension, hypercholesterolaemia as potential consequences of harmful work will be determined. Attention will be devoted to an analysis of the nature and significance of employees’ mental models of coping with stress. The present investigation attempts to identify those hazards which pose a threat to examined employees and to propose measures for medical surveillance, ergonomic recommendations and intervention strategy that mitigate adverse occupational stressors and outcomes.

Keywords: occupational health; occupational health psychology; stress at work; work conditions; workplace assessment; ergonomics; health effects; work-related diseases;  lifestyle; smoking; occupational safety