Biomedical subjects

M Chorazy

Publications and source records attributed to M Chorazy.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1992

Carrier DNA affects the integration of HSV-1 TK gene in the genome of L929TK- cells.

L929TK- cells were cotransfected with DNA mixtures containing tk gene of HSV-1, plasmids carrying LTR of MoMLV or RSV and carrier DNA of salmon sperm or chromosomal DNA of recipient cells. Selection of TK+ transformants was conducted in DMEM supplemented with HAT. Plasmids carrying LTR sequences of MoMLV or RSV retroviruses showed enhancing effect on the frequency of TK+ transformation. Southern blot analysis of chromosomal DNA of TK+ transformants demonstrated in clones deriving from cotransfections of tk gene and carrier DNA of L929TK- cells multiple copies of tk gene integrated into several genomic sites of host. Single copies of tk gene integrated into different sites of host genome occurred in chromosomal DNA of TK+ clones deriving from cotransfections of tk gene and carrier DNA of salmon sperm. Cells cotransfected with tk gene and plasmids carrying LTR sequences of MoMLV or RSV formed three dimensional colonies in semisolid agar medium. No effect of carrier DNA on the morphology of TK+ transformant clones was noticed.

Animals↗

PubMed1992

Expression of c-jun and Egr-1 genes in rat liver in response to partial hepatectomy, and injection of turpentine.

In rat liver stimulated by partial hepatectomy a significant expression of Egr-1 and to less extent c-jun genes was observed within 15-30 min after the surgery. The induction is transient and vanishes within one hour. Egr-1 and c-jun were also induced in liver after subcutaneous injection of turpentine, a strong inducer of acute phase response. A maximum activation of these genes was observed within 4-9 hours after administration of turpentine. Both Egr-1 and c-jun extend the list of "immediate early" genes involved in proliferative response and constitute a group of genes inducible at the beginning of acute phase response.

Acute-Phase Reaction↗

PubMed1991

Influence of airborne suspended matter on mitotic cell division.

The effect of organic extracts of airborne suspended matter collected in the highly polluted industrial region of Silesia (Poland) on mitotic cell division was evaluated in the Chinese hamster V79 cell line. Crude benzene extracts as well as sequential elution solvent chromatography (SESC) fractions were investigated for their ability to affect the mitotic index, the proportion of anaphases-telophases to metaphases (AT/M ratio), the cloning efficiency and to produce aneuploid cells. The incidence of cell division disturbances in V79 cells exposed to extracts increased in a concentration-dependent manner. Mitotic arrest, manifested as a highly increased mitotic index and a concomitant decrease in the AT/M ratio, was found for the crude extract at a dose corresponding to 0.75 m3 of air. Comparable effects were noticed for SESC fraction 4, probably containing monophenol compounds. A strong dose-dependent reduction of cloning efficiency of V79 cells demonstrated cytotoxic activity of both the crude extract and fraction 4.

Air Pollutants↗

PubMed1990

Aromatic DNA adducts in white blood cells of coke workers.

White blood cell DNA adducts were measured in coke workers, local controls and countryside controls using the 32P-postlabelling technique. The method detected aromatic adducts including those formed by polycyclic aromatic hydrocarbons (PAHs). Coke workers are heavily exposed to PAHs particularly when working at the batteries. A difference in adduct levels was noted between the coke workers at the battery as compared to other jobs. The adduct levels in the non-battery were higher than those in the countryside controls.

Air Pollutants, Occupational↗

PubMed1990

DNA adducts in human environmentally exposed to aromatic compounds in an industrial area of Poland.

The effect of environmental pollution on DNA adducts in humans was analysed in a highly industrialized area of Poland. Coded samples of white blood cell DNA were analysed by 32P-postlabelling and immunoassay from three populations: coke workers, exposed occupationally to high levels of polycyclic aromatic hydrocarbons (PAHs); residents of the towns around cokeries (local controls); and residents from rural Poland (countryside controls). Local controls exhibited adduct levels and patterns similar to those of coke workers, while the levels in rural controls were 2-3 times lower. The results, based on coded samples and two different assays, suggest that environmental pollution is likely to contribute to the adduct levels in local controls. Furthermore, the results show that the levels of aromatic adducts in white blood cell DNA do not linearily relate to ambient air levels of PAHs but other sources such as food may be important contributors.

Air Pollutants↗