Challenge-comet assay, a functional and genomic biomarker for precision risk assessment and disease prevention among exposed workers.

Advancements in genomic technologies have ushered application of innovative changes into biomedical sciences and clinical medicine. Consequently, these changes have created enormous opportunities to implement precision population/occupational disease prevention and target-specific disease intervention (or personalized medicine). To capture the opportunities, however, it is necessary is to develop novel, especially genomic-based, biomarkers which can provide precise and individualized health risk assessment.

Retrospective Biological Dosimetry at Low and High Doses of Radiation and Radioiodine Impact on Individual Susceptibility to Ionizing Radiation.

Iodine-131 (I-131) is often used in thyroid diagnostics and therapy. External and internal exposure to radioiodine can lead to molecular and cellular damage in peripheral blood lymphocytes. The aim of this study was to explore the influence of low and high doses of I-131 on susceptibility to ionizing radiation.

Can consumption of raw vegetables decrease the count of sister chromatid exchange? Results from a cross-sectional study in Krakow, Poland.

Background: Sister chromatid exchange (SCE) is a widely used sensitive cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results of human monitoring studies and cytogenetic damage have revealed that biological effects of genotoxic exposures are influenced by confounding factors related to life-style. Vegetable and fruit consumption may play a role, but available results are not consistent.

Evidence for exposure-induced DNA repair abnormality is indicative of health and genetic risk.

A recent focus has been targeted toward the development of functional biomarkers that can be used to predict disease more reliably. One such biomarker is the challenge assay for DNA repair deficiency. Briefly, the assay involves challenging lymphocytes in culture to a DNA damaging agent in vitro and determining the repair outcome in chromosome aberrations and/or DNA strand breaks.

Investigation of the genotoxic effect of pesticides on greenhouse workers' lymphocytes.

In the present study, the genotoxic effects of commonly applied pesticides were evaluated using the alkaline comet assay (pH > 13). The amount of DNA damage (% DNA in tail) in peripheral lymphocytes of 49 male agricultural workers from Southern Poland were measured and compared to 50 men from the same area who had no previous occupational exposure to pesticides. No statistically significant differences in basal DNA damage were found between the study groups.

Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries.

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.

Repair competence assay in studies of the influence of environmental exposure to c-PAHs on individual susceptibility to induction of DNA damage.

Previous results from studies performed in three European cities suggested a decrease in DNA repair efficiency observed in lymphocytes of subjects occupationally exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (c-PAHs). The aim of this study was to investigate whether a relationship between exposure to environmental c-PAHs and cellular vulnerability to the induction of DNA damage and its repair is confirmed in a pooled group of subjects from Prague, Kosice and Sofia. The investigated pool consisted of 144 subjects occupationally exposed to environmental c-PAHs, who were municipal policemen or bus drivers.

Exposure to environmental polycyclic aromatic hydrocarbons: influences on cellular susceptibility to DNA damage (sampling Kosice and Sofia).

The aim of this study was to investigate a possible influence of occupational exposure to carcinogenic environmental polycyclic aromatic hydrocarbons (c-PAHs) on cellular susceptibility to the induction of the DNA damage. Monitoring was performed and blood samples were collected from two groups of male subjects: occupationally exposed and matched controls. The group exposed to c-PAHs (average age of 35.

Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe.

A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations (chromosome type and chromatid type) are limited. A total of 6,430 healthy individuals from nine laboratories in Croatia, Hungary, Lithuania, Poland, and Slovakia, included in chromosomal aberration surveys performed during 1978-2002, were followed up for cancer incidence or mortality for an average of 8.5 years; 200 cancer cases were observed.

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans.

The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality.

[Influence of mercury vapors on lymphocytes in vivo and on their susceptibility to UV-C and X-rays, and repair efficiency in vitro].

Background: The aim of the study was to compare the levels of DNA and cytogenetic damage in lymphocytes from donors occupationally exposed to mercury vapors and from matched controls as well as their cellular susceptibility to radiation and capabilities to repair DNA damage induced by UV-C or X-ray exposures in vitro.

Materials And Methods: To estimate cytogenetic damage, the analysis of sister chromatid exchange frequency (SCE) was used, and to detect DNA damage the alkaline version of single cell gel electrophoresis (SCGE) was applied. To analyze cellular susceptibility, lymphocytes were exposed to 6 J/m2 of UV-C or irradiated with 2 Gy of X-rays.

Influence of environmental exposure to PAHs on the susceptibility of lymphocytes to DNA-damage induction and on their repair capacity.

The influence of occupational exposure to environmental carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) on DNA damage detected in lymphocytes of exposed people (city policemen) was studied. The cellular susceptibility to the induction of the DNA damage and the repair capacity of exposed donors are presented in comparison with matched controls. Monitoring was performed and blood samples (164 donors) were collected in Prague, Czech Republic, during the winter and summer seasons.

Molecular epidemiology studies of carcinogenic environmental pollutants. Effects of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on exogenous and oxidative DNA damage.

Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment.

Response to challenging dose of X-rays as a predictive assay for molecular epidemiology.

Human biomonitoring, as a tool to identify health risk from environmental exposures, has gained increasing interest especially in the areas of cancer risk assessment and response to therapy. Chromosome aberrations resulting from direct DNA breakage or from inhibition of DNA repair or synthesis, as measured in peripheral blood lymphocytes, have been used successfully in the assessment of environmental health. Susceptibility to the induction of genotoxicity has been evaluated by the use of an in vitro challenge dose of UV or X-rays.

Biomonitoring of four European populations occupationally exposed to pesticides: use of micronuclei as biomarkers.

This paper presents the results obtained within the framework of an EU research project aimed at investigating the relationship between occupational exposure to pesticides and the induction of cytogenetic damage. Populations from Greece, Spain, Poland and Hungary, all of them characterised by intensive agricultural activity, were the subject of the study. A total of 239 agricultural workers and 231 unexposed controls were examined for cytogenetic effects in lymphocytes of peripheral blood and exfoliated cells of the oral mucosa.