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A Varkonyi

Publications and source records attributed to A Varkonyi.

11 recordsLinked to original sources
PubMed2006

DNA adducts among asphalt paving workers.

OBJECTIVE: Asphalt is used extensively in the highway construction industry and contains a complex mixture of polycyclic aromatic hydrocarbons, some of which are known or suspected to be human carcinogens. Though numerous epidemiologic studies have described an excess cancer risk among asphalt workers, a causal relationship has not been established. Accordingly, the primary objective of this study was to use DNA adducts as a biomarker of biologically effective dose and determine whether DNA damage resulted from occupational exposure to asphalt among paving workers. METHODS: Over a 12 month period, four peripheral blood samples (spring, summer, fall and winter) were obtained from 49 asphalt paving workers (169 samples) and 36 non-paving construction workers (103 samples). The spring, summer and fall samples were collected during the work-season, whereas the winter samples were collected during the off-season (due to the seasonality of paving work). Mononuclear white blood cells were isolated and analyzed for DNA adducts via the (32)P-postlabeling assay and generalized linear models were used to evaluate the DNA adduct data. RESULTS: Among paving workers during the work-season, DNA adducts increased during each day of the workweek such that mean adduct levels were lowest on Mondays (3 adducts per 10(10) nucleotides) and highest on Fridays (46 adducts per 10(10) nucleotides). Additionally, a 3-fold difference in adduct burden was observed by paving task such that mean adduct levels were lowest among roller operators (7 adducts per 10(10) nucleotides) and highest among screedmen (23 adducts per 10(10) nucleotides). Using adducts as a measure of biologically effective dose, these findings (weekday trend and task-based differences) were consistent with a previous evaluation of absorbed dose in the same population. Adduct levels were not, however, higher among paving workers than among non-pavers. Adducts were also highest during the winter months, suggestive of a seasonal effect that has been observed in previous studies. CONCLUSION: These findings indicate that adduct burden increased throughout the workweek among paving workers, suggesting that DNA damage may be associated with occupational exposure to hot-mix asphalt. However, the lack of contrast with non-paving workers, as well as the seasonal variation warrants additional investigation.

Air Pollutants, Occupational↗
PubMed2002

Primary lymphoedema associated with xanthomatosis, vaginal lymphorrhoea and intestinal lymphangiectasia.

Primary lymphoedema associated with chylous reflux is a very rare clinical entity. We report a 3-year-old girl with unilateral lymphoedema, xanthomatosis and vaginal lymphorrhoea. Biopsy also revealed intestinal lymphangiectasia. This paper also presents a brief review of the literature and draws attention to the significance of the xanthomatous eruption in the diagnosis of a chylous reflux.

Child, Preschool↗
PubMed2001

Effect of simulated microgravity on human lymphocytes.

During space flight the function of the immune system changes significantly. Several papers reported that postflight the number and the proportion of circulating leukocytes in astronauts are modified (Leach, 1992), the in vitro mitogen induced T cell activation is depressed (Cogoli et al., 1985; Konstantinova et al. 1993) and there are detectable differences in cytokine production of leukocytes as well (Talas et al. 1983; Batkai et al. 1988; Chapes et al. 1992). One of the possible modifying forces is the microgravity condition itself. Our aim was to analyse mechanisms responsible for changing leukocyte functions in low gravity environment. For terrestrial simulation of microgravity we used a Rotary Cell Culture System (RCCS) developed by NASA. We investigated the effect of simulated microgravity on separated human peripheral blood mononuclear cells (PBMCs). We detected the populations of different cells by antibodies conjugated to fluorofors using a Flow Cytometer. Since space flight reduces the number of peripheral blood lymphocytes (Stowe et al., 1999) we supposed that apoptotic (programmed cell death) processes might be involved. This hypothesis was supported by the result of our earlier experiment demonstrating that simulated microgravity increased the level of secreted Tumor Necrosis Factor-alpha (TNFalpha, a known apoptotic signal molecule) significantly (Batkai et al. 1999).

Apoptosis↗
PubMed2000

Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells.

Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced (32)P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who were carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype. The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.

Aged↗
PubMed1999

Early age at smoking initiation and tobacco carcinogen DNA damage in the lung.

BACKGROUND: DNA adducts formed as a consequence of exposure to tobacco smoke may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer. To determine whether DNA adducts can be used as a "dosimeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. METHODS: We used the 32P-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cells from 54 of these patients. From the smoking histories, we identified exposure variables associated with increased DNA adduct levels by use of multivariate analyses with negative binomial regression models. RESULTS/ CONCLUSIONS: We found statistically significant interactions for variables of current and former smoking and for other smoking variables (e.g., pack-years [number of packs smoked per day x years of smoking] or years smoked), indicating that the impact of smoking variables on DNA adduct levels may be different in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In current smokers, recent smoking intensity (cigarettes smoked per day) was the most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically significant correlation (r=.77 [Spearman's correlation]; two sided P<.001) was observed between DNA adduct levels in blood mononuclear cells and lung tissue. IMPLICATIONS: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA adduct persistence or that young smokers may be markedly susceptible to DNA adduct formation and have higher adduct burdens after they quit smoking than those who started smoking later in life.

Age Factors↗
PubMed1999

The effect of simulated microgravity conditions on the TNF-alpha production by human PBMCS.

Our earlier space experiments demonstrated that the interferon production of human lymphocytes in microgravity is 4-8 times higher than those of the synchronous ground controls in vitro (Talas et al. 1983). These data suggested that the microgravity has a significant effect on cells. Since the possibilities to perform space-experiments are very limited and our study raised many interesting questions, we wished to simulate microgravity conditions in our laboratory. For this reason we purchased a Rotary Cell Culture System (RCCS) equipment to study different cell lines and human peripheral blood mononuclear cells (PBMCs) in experimental microgravity conditions. RCCS is a horizontally rotated bubble free culture vessel with membrane diffusion gas exchange. We report here an analysis of TNF-alpha (tumor necrosis factor-alpha) production by human PBMCs (control cultures exposed to simulated microgravity in RCCS). The cells were incubated in the presence or absence of either NDV (Newcastle Disease Virus) or one of the different forms (PHA-M or -P) of Phytohaemagglutinin.

Cell Culture Techniques↗
PubMed1997

Study of arsenic mutagenesis using the plasmid shuttle vector pZ189 propagated in DNA repair proficient human cells.

Arsenic is considered a human carcinogen and although it is non-mutagenic in bacterial or human cells, arsenic interacts synergistically with genotoxic agents in the production of mutations. To gain insight into the possible mechanisms of action of arsenic in mutagenesis we studied the effects of sodium arsenite exposure on UV mutagenesis using the pZ189 shuttle vector system in DNA repair proficient GM 637 human fibroblasts. The purpose of the study was to determine whether arsenic alone induces mutations in the supF gene and whether the combination of arsenic and UV irradiation leads to a yield of mutants greater than the sum of the arsenic or UV treatments alone. Treatment of fibroblasts for 72 h with 5.0 microM of sodium arsenite alone produced significant increases in the pZ189 mutant frequency; 1 and 2.5 microM arsenite were not mutagenic. UV irradiation (320 J/m2) increased the yield of mutants 3.5-fold above the background rate. When UV-irradiated plasmid was allowed to replicate in fibroblasts treated with 1, 2.5, or 5.0 microM arsenite, the yields of mutations were significantly greater (p < 0.01) than the yield expected if the effects of each treatment were simply additive. The greatest potentiation of UV-induced mutations (4.9-fold) was observed at 1 microM arsenite, a concentration that was neither mutagenic itself nor cytotoxic. Restriction digest and DNA sequencing analyses indicated that arsenite alone produces both large-scale rearrangements, frameshifts and base substitutions. Hotspots for deletions were observed to be associated with a previously reported deletion hotspot involving 5'-CpC and runs of cytosines. Base substitutions observed involved A:T-->T:A transversions. The results indicate that arsenite alone is mutagenic in human cells using the supF reporter gene. The pZ189 shuttle vector may provide a model to study the molecular nature of co-mutagenesis of arsenic and other environmental agents. Further characterization of arsenic's effects on DNA repair and mutational spectra may be useful in the development of molecular markers in studies of arsenic carcinogenesis in human populations.

Arsenic↗
PubMed1995

Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung.

The formation of carcinogen-DNA adducts within the respiratory epithelium is thought to be a critical factor in the induction of lung cancer from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological studies of cancer risk. The validity of measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in peripheral blood mononuclear cells (MNCs) was investigated by comparing the levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer patients with those detected in MNCs from the same individuals using the 32P-postlabeling assay. The associations of smoking history and intake of dietary antioxidants with adduct levels also were assessed. Tissue-specific, as well as common DNA adducts were detected in lung and blood; total MNC adduct levels were highly correlated with total lung adducts. After smoking cessation, adduct levels appeared to decay in both tissues at similar rates. Multivariate analyses (Poisson regression modeling) indicated that dietary antioxidant intake (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts in both the lungs and blood. Of all models tested, the optimal one for predicting lung adduct levels included the measure of blood MNC adduct levels only. Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of DNA adducts in respiratory tissue in molecular epidemiological studies.

Aged↗