Immunosuppressive therapy in the posttransplant period and skin cancer.

AIMS: To determine the incidence of malignancies in renal transplant recipients (RTRs) and to analyze the association between the risk of skin cancer and immunosuppressive regiments used in the posttransplant period. MATERIALS AND METHODS: A cohort study was performed on 797 RTRs. Standardized morbidity ratio (SMR) was calculated for the most common types of cancer developed in the posttransplant period and different types of immunosuppressive therapy used in the cohort. RESULTS: 192 cases of malignancies were diagnosed in 86 RTRs (10.8%). Nonmelanoma skin cancer (NMSC) was the most frequent type of cancer (SMR = 6.42, p = 0.000), followed by renal cancer (SMR = 5.9, p = 0.000), malignant melanoma (SMR = 2.59, p = 0.080), and prostate cancer (SMR = 1.21, p = 0.593). The risk to develop NMSC was significantly higher in the group where cyclosporine has been used besides tacrolimus, mycophenolatemophetil and steroids as well as in the group treated with the combination without cyclosporine (SMR = 9.62, p = 0.001 and SMR = 5.18, p = 0.000). Furthermore, the risk was significantly higher in RTRs receiving anti-thymocyte globulin within induction therapy (SMR = 4.14, p = 0.000). CONCLUSION: The preliminary results indicate that the risk of NMSC in RTRs is significantly higher than in the general population and thus emphasize the need to improve preventive strategies in the Czech transplant population.

Metabolic gene variants associated with chromosomal aberrations in healthy humans.

Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome-type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid-type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown. Here, we want to test whether variants in metabolic genes associate with CAs in healthy volunteers. Cases were considered those whose total CA (CAtot) frequency was >2% and for CSA and CTA the limit was >1%. Controls had lower frequencies of CAs. Functional polymorphisms in seven genes were selected for analysis: cytochrome P450 1B1 (CYP1B1), epoxide hydrolase 1 (EPHX1), NAD(P)H:quinone oxidoreductase 1 (NQO1), each coding for phase 1 enzymes, and glutathione S-transferase P1 (GSTP1), glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), coding for enzymes which conjugate reactive metabolites, that is, phase 2 enzymes. The number of volunteers genotyped for each gene varied from 550 to 1,500. Only EPHX1 was individually associated with CAtot; high activity genotypes decreased CAtot. A total of six significant (P < 0.01) pair-wise interactions were observed, most including a GST variant as one of the pair. In all genotype combinations with significant odds ratios for CAs a GST variant was involved. The present data provide evidence that variants in genes coding for metabolic enzymes, which individually have small effects, interact and are associated with CA frequencies in peripheral lymphocytes of healthy volunteers.

Relative Importance of Traditional Risk Factors for Malignant Melanoma in the Czech Population.

AIM: The Czech Republic is one of the leading European countries in incident cases of malignant melanoma (MM), which is on the rise. The study objective was to assess the strength of associations between MM and the known generally accepted risk factors for MM in the population of the Czech Republic. METHODS: The study was designed as a case-control study where cases were incident cases of MM detected at the Department of Dermatology and Venereology of the Bulovka Hospital. Controls were selected from cancer-free patients admitted to departments other than Dermatology and Venereology. Validated questionnaires were used to collect demographic, epidemiological, and clinical data. RESULTS: The binary logistic model shows the main risk factors for MM: male, female (OR=0.292, 95% CI=0.175-0.486), a changed mole (OR=6.371, 95% CI=3.774-10.756), a history of skin cancer (OR=95.704, 95% CI=37.241-10.756), and sunbeds use (OR=3.594, 95% CI=1.288-10.028). Using sunscreen products was considered as a protective factor against MM (OR=0.253, 95% CI=0.137-0.466). CONCLUSION: The primary and secondary prevention increasingly emerges as a public health priority in the effort to reverse the negative trend in cases of MM and mortality from this disease in the Czech Republic. A prerequisite for an effective secondary prevention through screening is, among others, the identification of the population groups at highest risk for MM.

Structural chromosomal aberrations as potential risk markers in incident cancer patients.

Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients.

Association of serum bilirubin and promoter variations in HMOX1 and UGT1A1 genes with sporadic colorectal cancer.

Heme oxygenase-1 (HMOX1) and bilirubin UDP-glucuronosyltransferase (UGT1A1) enzymes, both involved in bilirubin homeostasis, play an important role in the oxidative stress defense. The objective of our study was to assess the effect of promoter variations of HMOX1 and UGT1A1 genes and of serum bilirubin on the risk of sporadic colorectal cancer (CRC). This exploratory case-control study was based on 777 CRC patients and 986 controls from the Czech Republic. The (GT)(n) and (TA)(n) dinucleotide variations in HMOX1 and UGT1A1 gene promoters, respectively, were determined by fragment analysis. In addition, the A(-413)T variant in HMOX1 promoter was also analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum bilirubin levels were compared in a subset of 174 cases and 247 controls, for whom biochemical data were available. After adjustment for age, a significant association between CRC risk and UGT1A1*28 allele carrier status was detected [odds ratio (95% confidence intervals) = 0.80 (0.60-0.97), p = 0.022]. No association between CRC risk and individual HMOX1 gene variants was observed, although a diplotype analysis revealed an increased risk for a specific HMOX1 genotype combination. These effects were more pronounced in males. Substantially lower serum bilirubin levels were detected in CRC patients compared to the controls (p < 0.001); each 1 µmol/L decrease in serum bilirubin was associated with a 7% increase of CRC risk (p < 0.001). In conclusion, UGT1A1*28 allele carrier status might be a protective factor against the development of CRC in the male population, whereas low serum bilirubin levels are associated with an increased risk of CRC in both genders.

Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patients and healthy controls.

Alteration of DNA integrity is a potential cause of cancer and it is assumed that reduced DNA repair capacity and accumulation of DNA damage may represent intermediate markers in carcinogenesis. In this case-control study, DNA damage and nucleotide excision repair capacity (NER-DRC) were assessed in association with sporadic colorectal cancer (CRC). Both parameters were quantified by comet assay in blood cells of 70 untreated incident patients and 70 age-matched healthy controls. mRNA expression and polymorphisms in relevant NER genes were concurrently analyzed. The aim of this study was to characterize incident CRC patients for NER-DRC and to clarify possible relations between investigated variables. Comet assay and mRNA expression analysis showed that CRC patients differ in repair capacity as compared to controls. Patients had a lower NER-DRC and simultaneously they exhibited higher endogenous DNA damage (for both P < 0.001). Accumulation of DNA damage and decreasing NER-DRC behaved as independent modulating parameters strongly associated with CRC. Expression levels of 6 out of 9 studied genes differed between groups (P ≤ 0.001), but none of them was related to DRC or to any of the studied NER polymorphisms. However, in patients only, XPC Ala499Val modulated expression levels of XPC, XPB and XPD gene, whereas XPC Lys939Gln was associated with XPA expression level in controls (for all P < 0.05). This study provides evidence on altered DRC and DNA damage levels in sporadic CRC and proposes the relevance of the NER pathway in this malignancy. Further, alterations in a complex multigene process like DNA repair may be better characterized by functional quantification of repair capacity than by quantification of individual genes transcripts or gene variants alone.

DNA damage, DNA repair rates and mRNA expression levels of cell cycle genes (TP53, p21(CDKN1A), BCL2 and BAX) with respect to occupational exposure to styrene.

We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes. The workers were divided into low (<50 mg/m³) and high (>50 mg/m³) styrene exposure groups. We found negative correlations between mRNA expression of TP53, BCL2, BAX and styrene exposure (P < 0.001 for all parameters). In contrast, p21(CDKN1A) mRNA expression significantly increased with increasing styrene exposure (P = 0.001). SSBs and endonuclease III-sensitive sites increased with increasing mRNA levels of TP53 (P < 0.001 for both) and BCL2 (P = 0.038, P = 0.002, respectively), whereas the same parameters decreased with increasing mRNA levels of p21(CDKN1A) (P < 0.001, P = 0.007, respectively). γ-Irradiation-specific DNA repair rates increased with p21(CDKN1A) mRNA levels up to the low exposure level (P = 0.044). Our study suggests a possible relationship between styrene exposure, DNA damage and transcript levels of key cell cycle genes.

Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls.

BACKGROUND: The majority of human cancers arise from cells unable to maintain genomic stability. Recent prospective studies indicated that enhanced chromosomal aberrations (CAs) frequencies are predictive of gastrointestinal and lung cancers. However, studies on incident cancer patients are lacking; thus, we investigated chromosomal damage in newly diagnosed cancer patients and healthy individuals. METHODS: We analyzed chromosomal damage in peripheral blood lymphocytes in a group of 300 incident cancer patients (with different malignancies) in comparison with 300 healthy controls. RESULTS AND CONCLUSIONS: The frequencies of aberrant cells (ACs) and CAs were significantly higher in patients (2.38 +/- 1.56 and 2.53 +/- 1.69, respectively) as compared with controls (1.81 +/- 1.31 and 1.94 +/- 1.47, respectively, P < 0.01). The percentual difference in chromatid-type aberrations (CTAs) between patients and controls was moderately significant (1.37 +/- 1.20 and 1.11 +/- 0.99, respectively, P

Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers.

Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure. The workers were divided into low (below 50 mg/m³) and high (above 50 mg/m³)) styrene exposure groups. DNA damage and DNA repair capacity were analyzed in peripheral blood lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A significant negative correlation was observed between SSBs and styrene concentration at workplace (R=-0.38, p=0.001); SSBs were also significantly higher in men (p=0.001). The capacity to repair irradiation-induced DNA damage was the highest in the low exposure group (1.34±1.00 SSB/109 Da), followed by high exposure group (0.72±0.81 SSB/109 Da) and controls (0.65±0.82 SSB/109 Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated with styrene concentrations in blood and at workplace (p<0.001) and positively with SSBs (p<0.001). Micronuclei were not affected by styrene exposure, but were higher in older persons and in women (p<0.001). In this study, we did not confirm previous findings on an increased DNA repair response to styrene-induced genotoxicity. However, negative correlations of SSBs and mRNA expression levels of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted study.

NBN 657del5 heterozygous mutations and colorectal cancer risk in the Czech Republic.

The most frequent Nijmegen breakage syndrome (NBS)-causing mutation is a 5-base pair deletion in gene coding for nibrin (NBN 657del5), which results in a non-fully functional protein product and is particularly frequent in Central and Eastern Europe. Recent studies have investigated whether NBN 657del5 carriage may predispose to an increased risk of different types of cancer. The Czech Republic has one of the highest incidences of colorectal cancer in the world as well as high incidence of NBS. To assess whether NBN 657del5 associates with an increased risk of sporadic colorectal cancer, we have screened 771 colorectal cancer patients, 614 controls with negative colonoscopy and 818 healthy blood donors from the Czech Republic. There were no significant differences between the frequencies of heterozygous carriers among the three groups. The present results do not provide any evidence that the exceeding risk of CRC in this population is attributable to the high frequency of heterozygous carriage of the NBN 657del5.

Chromosomal aberrations in tire plant workers and interaction with polymorphisms of biotransformation and DNA repair genes.

We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.5+/-1.8% vs. 1.7+/-1.2%, respectively). The differences between groups (ANOVA) were borderline significant (F=2.6, P=0.055). Chromosomal aberrations were higher in subjects with GSTT1-null (2.4+/-1.7%) than in those with GSTT1-plus genotype (1.8+/-1.4%; F=7.2, P=0.008). Considering individual groups, this association was significant in smoking exposed workers (F=4.4, P=0.040). Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010). Both chromatid- and chromosome-type aberration frequencies were mainly affected by exposure and smoking status. Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1.25, P=0.081) polymorphisms. Chromosome-type aberrations were lowest in individuals bearing the EPHX1 genotype conferring the high activity (OR 0.38, 95%CI 0.15-0.98, P=0.045). Present results show that exposed individuals in the tire production, who smoke, exhibit higher chromosomal aberrations frequencies, and the extent of chromosomal damage may additionally be modified by relevant polymorphisms.

Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancer.

AIM: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D-PDS) for diagnostics of extraprostatic extension of prostate cancer. PATIENTS AND METHODS: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D-PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. RESULTS: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D-PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D-PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D-PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. CONCLUSION: Our data suggest that the 3D-PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension.

2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity.

Vascular function was examined in subjects with long-term high level of serum 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) during their follow-up visits. Their earlier mean peak TCDD level at the time of exposure in 1965-1968 was estimated in the range of 3300-74 000 pg/g lipids. Ten former pesticide production workers heavily exposed to TCDD (age 57 +/- 2 years, TCDD about 170 pg/g lipids) were examined in 2001. Extended group of 15 TCDD-exposed men (age 59 +/- 3 years, TCDD about 130 pg/g lipids) underwent the same examination in 2004. Findings were compared with a control group of 14 healthy men (age 54 +/- 2 years). Skin microvascular reactivity (MVR) was measured by laser Doppler perfusion monitoring in the forearm during post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH). Several parameters of MVR in men exposed to TCDD were significantly impaired, compared with the control group and further progression of the impairment of MVR has been observed between years 2001 and 2004. Serum concentration of E-selectin and inhibitor of tissue plasminogen activator 1 (PAI-1) was significantly higher in exposed subjects (56.0 +/- 18.4 ng/mL versus 40.0 +/- 12.0 ng/mL, P = 0.022 and 90.9 +/- 33.3 ng/mL versus 45.0 +/- 18.0, P = 0.002, respectively). In addition, PORH in the forearm was significantly negatively associated with SOD activity (r = -0.77, P = 0.009) as well as the velocity of perfusion increase during TH (r = -0.68, P = 0.03) and TH% (r = -0.78, P = 0.008). Our data document the presence of endothelial dysfunction in TCDD-exposed men.

Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels.

Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and beta2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 microg/L; mean, 78.4 microg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-beta-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children's renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals. Key words: arsenic, biomarkers, cadmium, dopaminergic, heavy metals, interactions, lead, mercury, renal.

Gastrointestinal comorbidities in patients with psoriasis in the Czech Republic: The results of 189 patients with psoriasis and 378 controls.

AIMS: The aim of the study was to investigate gastrointestinal comorbidities, identify risk factors and detect the early stages of autoimmune gastrointestinal diseases, such as Crohn's disease, ulcerative colitis and coeliac disease in patients with psoriasis. METHODS: This was a hospital-based case-control study. Patients with chronic plaque psoriasis were included as cases. The control group consisted of patients with other skin diseases and who complied with the same selection criteria as cases. Two controls were selected per one case. We analysed the following antibodies (ASCA, AEP, p-ANCA, AGC, EMA, ARA, tTG, AGA) and non-specific signs of gastrointestinal diseases. RESULTS: There were significant differences between cases and controls in several parameters. Leucocyte count, CRP, total protein, transglutaminase IgA antibodies and p-ANCA were statistically significant between groups (P < 0.05). In the binary logistic model, leucocyte count and p-ANCA (for all parameters included in the logistic model P ≤ 0.001) were associated with psoriasis. CONCLUSION: Patients with psoriasis should be regularly screened for coeliac and inflammatory bowel disease. Early diagnosis of gastrointestinal diseases and risk factors may prevent complications and greatly improve the patient's quality of life.

Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer.

There is evidence that increased frequency of chromosomal aberration (CA) in peripheral blood lymphocytes is a predictor of cancer, but further data are needed to better characterize CA as marker of cancer risk. From the archives of 15 laboratories we gathered cytogenetic records of 11,834 subjects who were free of cancer at the moment of blood drawing and who underwent cytogenetic examination for preventive purposes in the Czech Republic during 1975-2000. We linked these records to the national cancer registry, revealing a total of 485 cancer cases. Subjects were classified according to the percentiles of CA distribution within each laboratory as low (0-33rd percentile), medium (34-66th percentile), and high (66-100th percentile). Subjects were further classified by occupational exposure and by subclass of CA. We found a significant association between the overall cancer incidence and the presence of chromosome-type aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence interval (CI), 1.03-1.50] but not chromatid-type aberrations. Stomach cancer showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01-60.0). The predictivity of CA observed in subjects exposed to various classes of carcinogens did not significantly differ from the group of nonexposed subjects. This study contributes to validation of CA as a predictive marker of cancer risk, in particular, of stomach cancer; the association between CA frequency and cancer risk might be limited to chromosome-type aberrations.

Significantly higher incidence of skin cancer than other malignancies in patients after heart transplantation. A retrospective cohort study in the Czech Republic.

AIMS: To perform the first study in Czech Republic on heart transplant recipients (HTRs), compare the risks for different types of cancer and provide comprehensive analysis of skin cancer and other types of cancer morbidity from which we would be able to derive an evidence-based skin cancer surveillance program. MATERIALS AND METHODS: A retrospective cohort study was performed to determine and compare standardized morbidity ratio (SMR) of different types of cancer developed after heart transplantation. We analysed data obtained from medical documentation of 603 HTRs transplanted between 1993 and 2010. RESULTS: 191 incident cases of malignancy occurred in123 HTRs (20.4%). According to expectations, nonmelanoma skin cancer was the most frequent type of malignancy (119 cases) with SMR 7.6 (P < 0.001), followed by lung cancer with SMR 2.7 (P < 0.001). SMR for melanoma was 2.5, P = 0.129. Other types of cancer in HTRs (prostate and kidney cancer) were less frequent (SMR 2.06, P = 0.038 and SMR 2.03, P = 0.122). CONCLUSION: The risk of malignancy development is significantly higher for HTRs compared to the general population. Squamous cell carcinoma of the skin is the most frequent type of cancer followed by basal cell carcinoma. These findings emphasise the importance of regular skin cancer screening in HTRs.

Cytogenetic analysis using fluorescence in situ hybridization (FISH) to evaluate occupational exposure to carcinogens.

Chromosomal aberrations determined by conventional method or fluorescence in situ hybridization (FISH) technique with whole chromosome painting are used as biomarkers of effect. Groups occupationally exposed to 1,3-butadiene (BD), acrylonitrile, ethyl benzene and benzene in petrochemical industry, and carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) from ambient air were followed by conventional method and FISH painting for chromosomes # 1 and # 4, in total 383 subjects, including controls. No effect was observed by either method with exposure to 1,3-butadiene < 1mg/m(3) and acrylonitrile < 0.3mg/m(3). Ethyl benzene and benzene exposure significantly increased chromosomal aberrations by both methods, which decreased after the implementation of preventive measures. The genomic frequency of translocations by FISH calculated as FG/100 was significantly increased in city policemen versus control group exposed to c-PAHs from ambient air (1.72+/-1.57 versus 1.25+/-1.11, P<0.05). The method of FISH with whole chromosome painting seems to be more sensitive to detect chromosomal injury by occupational exposure to carcinogens than conventional method.

Cytogenetic analysis and occupational health in the Czech Republic.

This paper summarizes the experiences of the Czech Hygiene Service since the middle 1970s until the present time, using cytogenetic analysis as a biomarker of exposure. We have included a review of all the available scientific literature in Czech as well as in English, and have described the most important milestones in the history of the use of cytogenetic analysis in the Czech Republic. Details on the levels of occupational exposure and the corresponding observed frequencies of aberrant cells are provided. Furthermore, we discuss the interpretation of the cytogenetic findings in the context of occupational health and give several examples when the results of cytogenetic analysis provided the chief argument used to enforce improved working conditions and to establish safer maximum allowable concentrations.