Biomedical subjects

M Chorazy

Publications and source records attributed to M Chorazy.

At least 19 recordsLinked to original sources

PubMed1998

Bleomycin sensitivity test in the exposed and reference human populations.

Sensitivity to bleomycin was investigated in lymphocytes collected from three groups of males: 30 occupationally exposed cokery workers, 38 environmentally exposed Silesian citizen and 35 rural inhabitants. The data were analyzed at both the individual and group levels. The first analysis has revealed a substantial interindividual variability in the level of generated breaks (breaks per cell, b/c). This variability was independent of the age of the donor, smoking habit and X-ray exposure as tested in the multiple regression model. The means per group for the occupationally and environmentally exposed persons were almost the same with the values of 0.674 and 0.639, respectively. These two groups differed significantly from the rural population (b/c=0.448, p<0.001 by MANOVA). The reproducibility of the assay was satisfying (p>0.49 by the Wilcoxon matched paired test) after omitting 7 out of 49 repeatedly sampled donors. Those persons exhibited extremely high b/c rates in the first sampling.

Adolescent↗

PubMed1998

Modulation of DNA adduct levels in human mononuclear white blood cells and granulocytes by CYP1A1 CYP2D6 and GSTM1 genetic polymorphisms.

The CYP1A1, CYP2D6 and GSTM1 genes encode biotransforming enzymes involved in activation and detoxification of xenobiotics. Metabolically activated chemical compounds may interact with DNA and form adducts. In this study, the effect of the GSTM1, CYP1A1 exon 7 and CYP2D6 polymorphisms on DNA adduct levels was studied in 170 healthy volunteers. DNA adducts levels were measured by 32P-postlabelling in mononuclear white blood cells (WBC, lymphocytes and monocytes) and granulocytes collected in summer and winter. The influence of the genotype on the level of DNA adducts in both types of WBCs was observed only in summer samples. Individuals with GSTM1 deficient (null) genotype had significantly elevated level of adducts in mononuclear WBCs (p = 0.045) and granulocytes (p = 0.031) compared to GSTM1 positives. Higher adduct levels in carriers of combined GSTM1(null)/CYP1A1-Ile/Val genotype were found in both types of WBCs when compared to GSTM1(+)/CYP1A1-Ile/Ile genotype carriers (p = 0.046 in granulocytes, p = 0.092 in mononuclear WBCs). CYP2D6 wild-type homozygotes (EMs) and heterozygotes (HEMs) were shown to have significantly higher mononuclear WBC DNA adduct levels than mutant homozygotes (PMs) (p = 0.037 and p = 0.014). When confounding factors associated with PAH exposure were taken into account a statistically significant effect of CYP1A1 exon 7 polymorphism on DNA adduct levels was found (p = 0.012 in mononuclear WBCs, p = 0.043 in granulocytes). In a subgroup of current smokers (n = 95) high DNA adduct levels in granulocytes were associated with GSTM1(null) genotype, and increased adduct levels in mononuclear WBCs correlated with CYP2D6 EM and HEM genotypes. In winter samples the association between the genotype and DNA adduct levels was not observed.

Adult↗

PubMed1998

A molecular epidemiology study in women from Upper Silesia, Poland.

The present report is a follow-up to our previous molecular epidemiology studies on DNA damage in residents of the industrial region of Upper Silesia. The study was designed to focus on environmental exposure to airborne pollutants; other exposures or confounding factors (e.g. smoking status and age) were eliminated. A Silesian population consisting of 67 donors was compared to 72 inhabitants of a less polluted but similarly urbanized area, surrounded by a rural part of Poland. In both regions the donors were non-smoking females with similar age range, and occupation. Eight biomarkers including urinary mutagenicity and 1-hydroxypyrene, polycylic aromatic hydrocarbon PAH-DNA adducts in oral mucosa, sister chromatid exchanges (SCE), high frequency cells (HFC), chromosomal aberrations (CA), and sensitivity to bleomycin in lymphocytes as well as glutathione s-transferase (GSTM1)/cytochrome P4501A1 (CYP1A1) genotypes were evaluated in samples collected in summer and winter seasons. All the biomarkers of internal and biological doses of mutagens and their early biologic effects indicated statistically significant increases in the Silesian group when compared to the controls. Immunohistochemical quantitation of PAH-DNA adducts additionally revealed significant seasonal changes in the levels of adducts. No influence of susceptibility genotypes (GSTM1 and CYP1A1) on biomarker levels was observed.

Adult↗

PubMed1997

Sister chromatid exchanges and high-frequency cells in men environmentally and occupationally exposed to ambient air pollutants: an intergroup comparison with respect to seasonal changes and smoking habit.

Sister chromatid exchanges (SCE) and high-frequency cells (HFC) were measured in peripheral blood lymphocytes from men environmentally and occupationally exposed to a mixture of ambient air pollutants. The environmentally exposed individuals were inhabitants of the industrial region of Upper Silesia; those occupationally exposed were Silesian cokery or steel plant workers, while the control group consisted of rural region residents. A total of 147 males were enrolled in the study. Blood samples were collected in winter (February) and summer (September) seasons. Three major areas were investigated during the study: exposure-based dose dependency, seasonal changes, and influence of smoking habits on the SCE frequencies. The latter is frequently reported as a confounding factor in SCE analyses. In both winter and summer samples, statistically significant increases of SCE were observed in the environmentally and occupationally exposed groups compared to the controls (p < 0.001). The difference between both exposed groups was also significant (p < 0.001). An intergroup comparison was based on ANOVA after adjustment for smoking status. In all three groups of interest, a seasonal variation was found with higher levels in winter. However, in a part of the study in which each donor served as his own control, statistical differences were only found within the exposed groups. Control region inhabitants did not have significantly higher frequencies of SCE in winter, compared to summer samples. The impact of two major confounders, age of the donor and smoking habit, was investigated by multiple regression analysis. Smoking was a major factor influencing the level of SCE. Nevertheless, the effect was seen in winter samples only, which suggests an additive response and adds new information to this known effect.

Adolescent↗

PubMed1997

Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland.

OBJECTIVES: The interaction of benzo(a)pyrene with serum albumin was measured in an attempt to identify the actual exposure and to evaluate albumin adduct measurements as biomarkers for exposure monitoring. METHODS: Benzo(a)pyrene-diol-epoxide (BPDE)-albumin adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in plasma of coke oven plant workers from three plants and from people living in a highly industrialised area of Silesia in Poland. Due to the high air concentrations of polycyclic aromatic hydrocarbons (PAHs) in this area, a control group was selected from a rural non-industrialised area in Poland. Breathing zone air measurements of PAHs were collected from some of the participants. RESULTS: Coke oven plant workers and non-occupationally exposed people had similar concentrations of albumin adducts whereas the rural controls were significantly lower (2.74 fmol adducts/microgram albumin (SEM 0.124)). The mean concentration of BPDE-albumin adduct in plasma of both the occupational and the environmental groups were significantly higher in the summer samples (4.34 fmol adducts/microgram albumin (SEM 0.335) and 4.55 fmol adducts/microgram albumin (SEM 0.296), respectively) than in the winter samples (3.06 fmol adducts/microgram albumin (SEM 0.187) and 3.04 fmol adducts/microgram albumin (SEM 0.184), respectively) even though the air measurements showed higher concentrations of PAHs in the winter. The statistical analysis did not show any effects of air exposures on concentrations of BPDE-albumin adduct. CONCLUSIONS: A multiple regression analysis of the measured concentrations of BPDE-albumin adducts for all the groups, during both seasons, indicates that occupational exposures do not contribute significantly to the formation of adducts. In general, the concentrations of albumin adducts found vary within relatively small limits for the two seasons and between the various groups of participants. No extreme differences were found.

Adolescent↗

PubMed1996

Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers.

The p15(INK4B), p16(INK4) and p18 genes are members of the gene family coding for inhibitors of cyclin-dependent kinases 4 and 6. p15(INK4B) and p16(INK4) are located at 9p21, a chromosomal region frequently deleted in many human neoplasms. To examine the role of these 3 genes in lung carcinogenesis, somatic mutations within the genes were analyzed by single-strand conformation polymorphism and DNA sequencing in 71 non-small-cell lung cancer (NSCLC) samples. Six somatic mutations in the p16(INK4) gene and 3 cases with a polymorphic allele were observed. Loss of heterozygosity in the p18 gene was found in 1 sample. We did not find any intragenic mutations in the p15(INK4B) or p18 genes. We conclude that p16(INK4) mutations play a role in the formation of some NSCLCs, whereas the involvement of p15(INK4B) and p18 is uncommon.

Base Sequence↗

PubMed1996

32P-postlabelling of bulky human DNA adducts enriched by different methods including immunoaffinity chromatography.

DNA adducts in lymphocytes and granulocytes of men exposed occupationally and environmentally to high concentrations of aromatic compounds in air were measured by the 32P-postlabelling method. Adducts in the same samples were characterized using nuclease P1 enrichment, butanol extraction and immunoaffinity purification with an antiserum raised against benzo[alpha]pyrene diol epoxide (BPDE). Only part of the adducts found in human samples were extracted by butanol. It also seemed, that only a small part of them belonged to the group of polycyclic aromatic hydrocarbons (PAHs) recognised by the antibody. Relative content of hydrophobic adducts and those with a structure similar to PAHs was higher in winter samples (when exposure to aromatic chemicals in air was higher) in comparison to samples collected in summer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1996

Assessment of cancer hazard from environmental pollution in Silesia.

New concepts of cancer risk estimation have been developed during the past decade. Short-term bioassays dealing with mutagenicity and carcinogenicity of environmental samples are being replaced by more relevant molecular epidemiology studies. The general idea of using a battery of bioassays remains unchanged while the origin of tested samples is different. Instead of testing samples collected from the environment, body fluids or human cells from exposed populations are under investigation. This paper reviews the collaborative study on cancer risk assessment in highly polluted industrial region of Silesia in which both approaches had been employed during the 1985-1995 period. A potent carcinogenic activity of airborne pollutants was indicated in a battery of in vitro and in vivo short-term assays. These studies were followed by the molecular epidemiology study performed on human populations inhabiting the region of Silesia. An elevated damage of genetic material on the chromosome and/or DNA levels was observed in the Silesian populations as compared with proper rural controls.

Air Pollutants↗

PubMed1996

Seasonal variation of DNA adduct pattern in human lymphocytes analyzed by 32P-HPLC.

32P-HPLC is a recently published method to generate DNA adduct profiles after exposure to a complex of genotoxic substances. The low detection limit enables characterization of individual DNA adducts in the general population. The 32P-HPLC method was applied to human lymphocytes and granulocytes from Silesia, a polluted industrial region in the south of Poland. Human samples were collected at the end of winter and summer to investigate the seasonal influence on DNA adduct formation. In lymphocytes a strong seasonal variation was seen in total DNA adducts, with winter values exceeding the summer values by 7.33 +/- 3.56 times. Granulocytes did not show any seasonal variation. In winter-collected lymphocytes the DNA adduct levels were 21.4 +/- 16.6/10(8) normal nucleotides (NN) while the summer values were 2.96 +/- 2.46/10(8) NN. Granulocytes had 8.06 +/- 7.76 and 9.59 +/- 6.19 DNA adducts/10(8) NN during winter and summer respectively. The lymphocyte DNA adduct profile consisted of at least 16 individual or clusters of DNA adducts. All 16 had a clear winter influence, with a winter:summer ratio of 1.6-15.3, indicating exposure to a complex mixture of genotoxic substances. The DNA adducts analyzed in human lymphocytes had retention times similar to DNA adducts generated by polycyclic aromatic hydrocarbons. The suggested candidates for DNA adducts displayed a similar seasonal variation in airborne particles to that found in DNA adducts in lymphocytes of humans living in the area. This is the first application of the 32P-HPLC method to analysis of DNA adducts in human tissues.

Air Pollutants↗

PubMed1996

DNA adducts in environmental, occupational and life-style studies in human biomonitoring.

The importance of DNA adducts in carcinogenesis had been discussed. The 32P-postlabelling method was developed as a quantitative technique to measure the level of different DNA adducts including adducts in human DNA. The elevated level of DNA adducts was found in white blood cells in persons exposed environmentally and occupationally to high concentrations of PAHs (polycyclic aromatic hydrocarbons) in the ambient air. Tobacco also generated higher level of DNA adducts both in lymphocytes and laryngeal tissues of smokers. Exposure to styrene has been of interest world-wide because of the very high exposure and persistence of adducts in DNA of lamination workers.

Air Pollutants↗

PubMed1996

Impact of environmental pollution on chromosomes and DNA of inhabitants of Upper Silesia.

Highly industrialized and densely inhabited region of Upper Silesia, Poland, presents an area of ecological disaster. Air quality is bad, and does not meet any quality standards. In peripheral blood white cells, the level of chromosomal aberrations, sister chromatid exchanges and DNA-adducts in adult, male individuals exposed to environmental pollution exceed values found for males in non-industrialized region.

Adult↗

PubMed1995

Immunohistochemical quantitation of polycyclic aromatic hydrocarbon-DNA adducts in human lymphocytes.

The formation of polycyclic aromatic hydrocarbon-DNA adducts was studied in peripheral blood lymphocytes obtained from men with occupational and environmental exposure. Subjects included coke factory workers, residents from the vicinity of the cokery, and rural region inhabitants (16 individuals in each exposure group). Adducts were determined by immunohistochemical analysis using a polyclonal antiserum recognizing benzo(a)pyrene and related polycyclic aromatic hydrocarbon diol epoxide-DNA adducts, a biotinylated secondary antiserum, and streptavidin-conjugated FITC. Propidium iodide was used to quantitate nuclear DNA. Dual fluorescence intensities were simultaneously measured with a Zeiss Axiovert microscope and a Bio-Rad MRC-600 argon laser scanning confocal attachment. Adducts were significantly elevated (P < 0.001) in both occupational and environmental groups, as compared to the rural control group by Mann-Whitney U test. The distribution of the data indicated the existence of cells with relatively higher adduct levels. The percentages of these so called "higher adduct-level cells" were 13.6, 11.5, and 3.7 in cokery workers, environmentally exposed individuals, and rural controls, respectively. The immunohistochemical method allows visualization and relative quantitation of polycyclic aromatic hydrocarbon-DNA adducts in individual lymphocytes. It requires a much smaller amount of blood than the previously used 32P-postlabeling and ELISA methods, which used isolated bulk DNA. It can also be used for adduct quantitation in biopsy material. The results of this pilot study indicate that this technique is a promising addition to biomonitoring studies.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1995

Biological monitoring of polycyclic aromatic hydrocarbon exposure in a highly polluted area of Poland.

Air pollution in Poland and particularly in Silesia is among the worst in Europe. Many coal mines and coke oven plants are located in this area, representing a major source of carcinogenic polycyclic aromatic hydrocarbons (PAHs). We quantitated the PAH exposure level in air samples using personal sampling devices, collected urine samples from the same individuals, and measured 1-hydroxypyrene with high performance liquid chromatography. Samples were collected twice, once in February and once in September. Mean PAH level of samples collected at three different coke oven plants varied from 2.3 micrograms/m3 to 12.3 micrograms/m3; the lowest mean was in September. Mean levels of 0.15 micrograms/m3 (September) and 0.44 micrograms/m3 (February) were noted for the environmentally exposed group. Mean urinary 1-hydroxypyrene varied from 2.45 to 13.48 mumol/mol creatinine at the three coke oven plants. The corresponding variation between the three different environmentally exposed groups in Silesia was 0.41-1.54 mumol/mol creatinine. In the nonindustrialized area, the mean varied from 0.20 to 0.14 mumol/mol creatinine. Seasonal variation was found both at the coke oven plants and in the environmental exposed groups in Silesia. Both PAH levels and 1-hydroxypyrene varied seasonally among coke oven workers and the environmentally exposed group. Our study shows that PAH exposure in the industrialized area of Silesia is high compared to levels in Western Europe. 1-Hydroxypyrene excretion in environmentally exposed individuals in Poland is among the highest in Europe.

Adult↗

PubMed1995

[Evaluation of thyroid anti-membrane and anti-thyroglobulin antibody determination in patients with thyroid cysts treated with external drainage under ultrasonographic control].

In patients (43 women and 12 men) external open drainage under ultrasonography control was performed. In 25 cases contents of serous nature, in 27 cases of colloid and in 3 cases of suppurative character were obtained. Anti-membrane thyroid antibodies (ATMA) and anti-thyroglobulin antibodies (Tg-Ab tire) were determined in the cyst contents as well as in the serum. The antibodies were present in the serum of 48% of the patients with serous cyst and in 52% with colloidal cysts. In serous cyst contents, ATMA and Tg-Ab antibodies were present in 52% of cases, while in the colloidal contents ATMA antibodies were found in 60% of patients and Tg-Ab antibodies in 68%. In 3 patients with cysts containing pus no antibodies were found. When antibodies were detected in the contents of serous and colloidal cysts their presence were also found in the serum. Among 55 cases with thyroid cysts, the antibodies were found in the serum of 47% of patients. The results indicate involvement of immunological factors the role of which has not been explained.

Adult↗

PubMed1994

Ambient air pollutants in upper Silesia: partial chemical composition and biological activity.

The air monitoring system in Upper Silesia has provided abundant data on airborne pollutants. Air quality in this region is bad: a concentration of several gases, volatile compounds, metals, and complex mixtures of organic compounds carried by small particulate matter exceeds both daily and yearly admissible levels. About 250 individual polycyclic aromatic hydrocarbonds (PAHs) were identified in airborne pollutants, and hundreds of not identified compounds are seen on gas chromatographic profiles as minor peaks. Among PAHs are present compounds with known carcinogenic potency for humans. Seasonal variation with distinctly lower concentration of pollutants in summer than in winter was noticed. Fifteen PAHs including benzo[a]pyrene (B[a]P) determined by GC-MS method in 20 measuring points showed constant relative proportions. Thus B[a]P could be used as a representative compound for other PAHs. In urban areas, a core of Silesia values for B[a]P concentration ranged from 60 to 90 ng/m3 in winter to 5 to 20 micrograms/m in summer. Mutagenicity tested on Salmonella strains showed seasonal variation with distinctly higher values in winter. Environmentally exposed humans showed a higher level of PAH-DNA adducts in WBC than the control population from rural area. Total organic extract of small particulate matter exhibited both direct and indirect mutagenic activity, induced formation of micronuclei in bone marrow cells of BALB/c mice, induced chromosomal rearrangements, and increased sister chromatid exchange index.

Air Pollutants↗

PubMed1994

[Cystic hepatic malignant tumors].

Non-parasitic hepatic cysts are common finding at abdominal sonography and in vast majority they are benign lesions. We report two cases of cystic liver neoplasms, namely the biliary cystadenocarcinoma and malignant hemangioendothelioma. In both cases, despite slow development of the tumour the presence of cyst considerably delayed diagnosis and hindered surgical treatment. We believe that more aggressive approach in "atypical" hepatic cysts could improve prognosis in such cases.

Adult↗

PubMed1993

Seasonal variation of aromatic DNA adducts in human lymphocytes and granulocytes.

DNA adducts were measured by 32P-postlabelling in lymphocytes and granulocytes of 75 healthy men exposed occupationally and environmentally to high concentrations of aromatic compounds in the ambient air. Volunteers enrolled in the study were men working at the coke batteries and nonoccupationally exposed inhabitants of Silesia, a highly industrialized region in southern Poland. Blood samples were drawn twice: in February and September 1992. Seasonal variations in the levels of DNA adducts were found only in lymphocytes: 3.6- and 8.7-fold in the occupationally and environmentally exposed groups respectively. In smokers the seasonal variation was as large as 12.8-fold in the environmentally exposed group. No seasonal variations were observed in granulocytes. The observed seasonal variation in the level of aromatic DNA adducts coincided with winter/summer differences in the concentrations of benzo[a]pyrene in the ambient air of Silesia. The study recommends the application of lymphocytes for adduct studies in chronic exposures and provides evidence on the repair of aromatic adducts in lymphocytes.

Benzo(a)pyrene↗

PubMed1992

A cytogenetic study of men environmentally and occupationally exposed to airborne pollutants.

The level of sister-chromatid exchanges (SCE), high-frequency cells (HFC), chromosomal aberrations (CA) as well as the proliferation rate index (PRI) were measured in peripheral blood lymphocytes from three groups of volunteers. The environmentally exposed donors were residents from the vicinity of a coke factory; the occupationally exposed persons were cokery workers, while rural region inhabitants served as a control group. Compared with the control group, statistically significant increases of SCE and HFC, as well as decreased cell kinetics (PRI) were observed for both occupationally and environmentally exposed groups. The effect was especially pronounced when only smokers were taken into account. A statistically significant increase of CA was observed in the environmentally exposed group when CA including gaps (CA + G) were evaluated. The proportion of HFC was found to be the most sensitive method to detect genetic effects on the tested human population. This study demonstrates the usefulness of all 4 biomarkers (SCE, HFC, CA and PRI) in monitoring populations exposed to ambient pollution and clearly indicates effects from residential as well as occupational exposure to industrial air pollutants.

Air Pollutants, Occupational↗