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 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold

Application of ionizing radiation in studies of biomarkers of individual susceptibility

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 diseases treatment. Chromosome aberrations resulting from direct DNA breakage or from inhibition of DNA repair or synthesis, measured in peripheral blood lymphocytes, have been used successfully in the assessment of health risk associated to environmental genotoxic exposures. A faster but sensitive and reliable method for detection of DNA damage, or DNA repair capacity, might be crucial to many fields from molecular epidemiology and toxicology to preventive and clinical medicine. There are reports that results of DNA measures with the use of single cell gel electrophoresis (SCGE) correlate, on the one hand, with physical measures of genotoxins, and on the other hand, with cytogenetic damage that is a biomarker associated to the alteration of the health risk. This review is based on studies in which exposure to radiation was applied as a challenging treatment and DNA damage induced and repaired was analyzed with the use of the alkaline version of SCGE assay. Results from studies on susceptibilities and repair competence carried out in various groups of exposed workers, controls, and cancer patients (more than 700 donors) show variability between donors both in a response to challenging treatment and in the efficiency of repair process. Influences of the occupational exposures and factors depending on genotypes or life style on cellular capacities are observed. Discussed results suggest that study in vitro with the challenging cells by radiation exposure and measuring, with the SCGE assay, the DNA damage before and after repair, may develop a good biomarker of the individual susceptibility to various genotoxins and exposures (environmental, occupational, therapeutic). Such a biomarker may have a potential use in a molecular epidemiology and preclinical identification

Biological efficiency of the Brookhaven Medical Research Reactor mixed neutron beam estimated from gene mutations in Tradescantia stamen hair cells assay

The relative biological effectiveness of low energy neutrons for the induction of various abnormalities in Tradescantia stamen hair mutation (Trad-SH) assay was studied using two clones (T-4430 and T-02), heterozygous for flower color. Dose response relationships for gene mutations induced in somatic cells of Trad-SH were investigated after irradiation with a mixed neutron beam of the Brookhaven Medical Research Reactor (BMRR), currently used in a clinical trial of boron neutron capture therapy (BNCT) for glioblastoma. To establish the RBE (relative biological effectiveness) of the BMRR beam in the induction of various biological end-points in Tradescantia, irradiation with various doses of g-rays was also performed. After irradiation all plants were cultivated several days at Brookhaven National Laboratory (BNL), the transported to Poland for screening the biological end-points. Due to the post-exposure treatment, all plants showed high levels of lethal events and alteration of the cell cycle. Plants of clone 4430 were more reactive to post-treatment conditions, resulting in decreased blooming efficiency that affected the statistics. Slope coefficients estimated from the dose response curves for gene mutation frequencies allowed the evaluation of ranges for the maximal RBE values of the applied beam vs. g-rays as 6.0 and 5.4 for the cells of T-02 and T-4430, respectively. Estimated fraction of doses from neutrons and corresponding biological effects for the clones T-02 and T-4430 allowed to evaluate the RBE values for neutrons part in the beam as 32.3 and 45.4, respectively

Occupational exposure influence on cancer risk biomarkers evaluated by FISH in Prostate Cancer or BPH patients

Benign prostatic hyperplasia (BPH) and prostate cancer (PC) became one of the most common males diseases. Environmental factors that affect prostate cancer susceptibility are poorly defined, although it is believed that occupational factors including: pesticides, ionising radiation, polycyclic aromatic hydrocarbons (PAHs) may be associated with the occurrence of prostate cancer. The aim of this study was to compare the cellular vulnerability to the induction by challenging dose of the aberrations in chromosome 1 and to find out whether it is associated to the category of prostate diseases, endogenic or egzogenic factors, and if could be considered in modeling a therapeutic procedure. We have examined cells in metaphase using FISH (Fluorescence in Situ Hybridization). Our results showed significant higher level of all aberrations in patients with prostate cancer compared to BPH stage group. Additionally, obtained results showed differences in susceptibility to radiation, between occupationally exposed and unexposed donors from prostate cancer patients and BPH stage groups, expressed in significantly elevated or lowered frequency of various aberrations. We have also studied influence of genetic predisposition on lymphocytes susceptibility to the X-ray induced DNA damage in donors lymphocytes. We have found that for all patients who had reported occurrence of cancers in a immediate family members had statistically higher level of all aberrations. This results may suggest existing relation between radiosensitivity of lymphocytes and increased prostate cancer risk. It may confirm hypothesis that prostate cancer risk increases in a consequence of genetic predisposition to instability and accumulation of various mutation resulting from occupational and environmental exposures

Efficiency of a 252Cf source in normal or in B-10 enriched lymphocytes evaluated by SCGE assay, classical cytogenetics and FISH technique

Biological effectiveness of a californium-252 source was evaluated after irradiations in vitro of normal or pretreated cells with compound enriched in the B-10 ion (Na210B12H11SH also known as BSH) in order to check the possibility of any enhancement effect due to the process of boron neutron capture. Peripheral blood lymphocytes were used as a model for human cells. Human blood samples or isolated lymphocytes were irradiated with the isotopic source of 252Cf, at the Faculty of Physics and Nuclear Techniques at the University of Mining and Metallurgy, Kraków, (both the neutron source and the samples were placed in an "infinite" polyethylene block). DNA and chromosomal damage were studied to compare the biological effectiveness of irradiation. Single cell gel electrophoresis also known as the Comet assay was done to investigate the DNA damage. Classical cytogenetic analysis was applied to assess the frequencies of unstable aberrations (dicentrics, rings and acentric fragments). To evaluate the frequencies of stable aberrations the fluorescence in situ hybridisation (FISH) with probes for chromosomes 1, 4 (14,3% of the whole genome) was performed. Linear (or close to linear) increases with radiation doses were observed for the DNA damage and aberration frequencies in lymphocytes both untreated or pretreated with BSH. Levels of translocations evaluated for the whole genome were comparable with the frequencies of dicentrics and rings. No significant differences were detected due to radiation dose in the frequencies of sister chromatid exchanges (SCE) detected in the second mitosis. Statistically no significant differences were observed in various biological end-points between normal or boron pre-treated cells