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  • 1
    Electronic Resource
    Electronic Resource
    Genetische Suszeptibilität im Hinblick auf toxische Arbeitsplatz- und Umweltbelastungen (1999)
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 42 (1999), S. 834-840 
    Details
    ISSN: 1437-1588
    Keywords: Schlüsselwörter Fremdstoffmetabolismus ; Polymorphismus ; Cytochrom P450 ; Glutathiontransferase (GST) ; N-Acetyltransferase (NAT2) ; Key words Xenobiotic Metabolism ; Polymorphism ; Cytochrome P450 ; Glutathione Transferase (GST) ; N-acetyltransferase (NAT2)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The variability of genes coding for xenobiotic metabolizing enzymes is an important reason for individual variations in susceptibilities towards chemical toxicants. In environmental and occupational medicine, polymorphisms of different isoforms of cytochrome P450, of N-acetyl-transferase (NAT2) and of glutathione transferase (GSTT1, GSTM1) are now of importance. In particular, the cytochrome P450 isoenzyme CYP2E1 is a key enzyme of the oxidative metabolism of highly relevant industrial chemicals as it metabolizes alkenes as well as aromatic and halogenated hydrocarbons. The influence of N-acetyltransferase 2 (NAT2) on the carcinogenic effect of aromatic amines upon the urothelium has been well established; the N-oxidation of aromatic amines leading to toxic and carcinogenic intermediates is higher in „slow” compared to „rapid” acetylators. In general, it is now evident that polymorphisms of xenobiotic metabolizing enzymes may have a decisive role in modulating the effects of toxicants on humans. Further progress in this field is to be expected, and calls for intensive discussion of both the preventiv and sociopolitical aspects.
    Notes: Zusammenfassung Eine wichtige Ursache individuell unterschiedlicher Ansprechbarkeiten gegenüber Fremdstoffen liegt in der Variabilität der Gene, die für fremdstoffmetabolisierende Enzyme kodieren. Für die Arbeits- und Umweltmedizin sind vor allem Polymorphismen verschiedener Isoformen des Cytochrom P450, der N-Acetyl-Transferase (NAT2) und der Glutathiontransferase (GSTT1, GSTM1) wichtig geworden. Aus arbeitsmedizinischer Sicht erscheint das Cytochrom P450 Isoenzym CYP2E1 als Schlüsselenzym des oxydativen Stoffwechsels vieler bedeutsamer Grundchemikalien der chemischen Industrie; es oxydiert eine Reihe von Alkenen, Aromaten und halogenierten Kohlenwasserstoffen. Die Isoenzyme der Glutathiontransferase GSTT1 und GSTM1 sind wichtig im Metabolismus von organischen Lösemitteln, Kunststoffmonomeren und Intermediaten polyzyklischer aromatischer Kohlenwasserstoffe. Der Einfluß der N-Acetyltransferase 2 (NAT2) bei der Auslösung von Urothelkarzinomen bei Exposition gegen aromatische Amine hat als erwiesen zu gelten; die N-Oxidation aromatischer Amine, die zu deren „Giftung” führt, wird bei „langsamen” Acetylierern vermehrt beschritten. Es ist insgesamt evident, daß Polymorphismen fremdstoffmetabolisierender Enzyme die Wirkungen toxischer Stoffe entscheidend modulieren. Bei weiter zu erwartendem Fortschritt der Erkenntnisse auf diesem Gebiet werden sich hieraus ergebende präventivmedizinische und soziopolitische Aspekte verstärkt zu diskutieren sein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001030050204
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  • 2
    Electronic Resource
    Electronic Resource
    Untersuchung zur klinischen Relevanz der Acetyliererphänotypisierung bei 196 Urotheltumorpatienten (1997)
    Springer
    Der Urologe 36 (1997), S. 64-67 
    Details
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Harnblasenkarzinom ; Aromatische Amine ; N-Acetyltransferase-2 ; Histopathologischer Befund ; Prognose ; Key words Bladder cancer ; N-Acetyltransferase 2 ; Histopathological grading ; Invasiveness ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A total of 196 patients with urothelial tumours were phenotyped for N-acetyltransferase 2 by the molar ratio of two caffeine metabolites excreted in urine. The proportion of “slow” acetylators, who are genetically predisposed to urothelial tumours if they have been exposed to aromatic amines in the past, in the entire group was 55 %, within the range in a normal population. Among 40 patients with assumed former occupational exposure to aromatic amines, 65 % were “slow” acetylators. Invasiveness, histopathological grading of the urothelial tumour at the time of first diagnosis, and course were not related to acetylator phenotype.
    Notes: Zusammenfassung Bei 196 Patienten mit urothelialen Tumoren wurde der Acetyliererphänotyp mittels zweier im Harn ausgeschiedener Koffeinmetabolite bestimmt. Der Anteil der „langsamen“ Acetylierer, die bei Exposition gegen aromatische Amine hinsichtlich der Entstehung eines Harnblasentumors prädisponiert sind, weicht mit 55 % im Gesamtkollektiv nicht von der Verteilung in der normalen Bevölkerung ab. Personen mit anzunehmender beruflicher Exposition gegen aromatische Amine (n = 40) weisen mit 65 % einen höheren Anteil „langsamer“ Acetylierer auf. Die Ausdehnung des Tumors bei Erstdiagnose, das histopathologische Grading und auch der Verlauf der Harnblasentumore der Klassifikation T1G1 und T1G2 waren unabhängig vom Acetyliererstatus. Der Acetyliererstatus erlaubt somit keine Aussage über die Prognose von Urotheltumoren.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001200050068
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  • 3
    Electronic Resource
    Electronic Resource
    Occupational risk factors for bladder cancer. A case-control study (1999)
    Springer
    Der Urologe 38 (1999), S. 358-363 
    Details
    ISSN: 1433-0563
    Keywords: Key words Bladder neoplasm • Smoking • Occupational risk factors • Painters • Mining ; Schlüsselwörter Harnblasenkarzinom • Rauchen • Berufliche Risikofaktoren • Maler • Bergbau
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ziel dieser Fallkontrollstudie an 412 männlichen Harnblasenkarzinompatienten und 414 Patienten mit benigner Prostatahyperplasie als Kontrollgruppe war die Identifizierung von Berufsgruppen mit einem erhöhten Harnblasenkarzinomrisiko in einer Montanregion. Raucher waren in der Gruppe der Harnblasenkarzinompatienten mit 58,3 % deutlich überrepräsentiert (Kontrollgruppe: 35,2 %), während der Anteil von Patienten, die das Rauchen seit mindestens 10 Jahren eingestellt hatten, in Fall- und Kontrollgruppe nahezu gleich war (10,2 % der Fälle, 9,7 % der Kontrollgruppe). Signifikant erhöhte Raucher-korrigierte „odds ratios“ (MH) fanden sich für Maler und Lackierer (MH 2,24, 95 % KI 1,07–5,13), Chemieberufe (MH 2,44, 95 % KI 1,05–5,67), Kokereiarbeiter (MH 2,89, 95 % KI 1,16–7,16) und Bergleute (MH 2,33, 95 % KI 1,52–3,58). Signifikant erniedrigte Raucher-korrigierte Risiken wiesen die kaufmännischen (MH 0,64, 95 % KI 0,45–0,92) und die Verwaltungsberufe (MH 0,58, 95 % KI 0,41–0,81) auf, für die berufsbedingte Expositionen gegen Harnblasenkarzinogene nicht anzunehmen sind.
    Notes: Summary Aim of this case-control study, performed on 412 male bladder cancer cases and 414 controls with benign prostatic hyperplasia in a former area of coal, iron and steel industries in Germany, was to identify occupations with an increased bladder cancer risk. In bladder cancer cases, smokers were overrepresented (58.3 %) compared to controls (35.2 %). The percentage of patients who had stopped smoking for at least 10 years did not differ in cases (10.2 %) and controls (9.7 %). Significantly elevated smoking-adjusted bladder cancer odds ratios (MH) were observed in painters and lacquers (MH 2.24, 95 % CI 1.07–5.13), chemistry-related occupations (MH 2.44, 95 % CI 1.05–5.67), coke plant workers (MH 2.89, 95 % CI 1.16–7.16) and hard coal miners (MH 2.33, 95 % CI 1.52–3.58). Significantly decreased smoking-adjusted bladder cancer odds ratios (MH) were observed in businessmen (MH 0.64, 95 % CI 0.45–0.92) and office personnel (MH 0.58, 95 % CI 0.41–0.81). In these two groups a relevant exposure to occupational bladder carcinogens is not likely.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001200050298
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  • 4
    Electronic Resource
    Electronic Resource
    A comparative study on different methods for the determination of energy expenditure (1990)
    Springer
    International archives of occupational and environmental health 61 (1990), S. 101-103 
    Details
    ISSN: 1432-1246
    Keywords: Energy expenditure ; Douglas Bag ; Kofranyi-Michaelis respirometer ; Oxylog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to determine energy expenditure, the Douglas Bag technique (DB) and Kofranyi-Michaelis respirometers (KM) have been widely used under field conditions for several decades. Some years ago the Oxylog (OX) method was developed, measuring simultaneously the difference of partial oxygen pressure in inspired and expired air (PO2 diff.) by two polarographic oxygen sensors. In order to compare these three methods laboratory experiments (3 test subjects, 5 different bicycle ergometer work loads, 180 measurements per apparatus) were performed. Oxygen uptake (VO2) varied between about 0.9 to 3.01/min. The VO2data obtained by the DB method, which were used as a reference, and those obtained by the KM method agreed fairly well. The recorded data of OX underestimated VO2up to 21%, with the deviation increasing with work intensity. A sufficient accuracy of recorded VO2 was observed only up to moderate work intensity. OX data calculated from ventilation volume of inspired air per minute (V1) and PO2 diff., measured by OX, were always about 19% higher than those recorded by OX. This means that the calculated VO2 values of the OX corresponded fairly well with DB values at heavy work loads. The reason for the differences between recorded and calculated OX data is still unknown. Further research is urgently needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00397856
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  • 5
    Electronic Resource
    Electronic Resource
    A note on individual differences in the urinary excretion of optical enantiomers of styrene metabolites and of styrene-derived mercapturic acids in humans (1995)
    Springer
    Archives of toxicology 69 (1995), S. 300-305 
    Details
    ISSN: 1432-0738
    Keywords: Key words Styrene ; Mandelic acid enantiomers ; Styrene-specific mercapturic acids ; Individual metabolic variation ; Enzyme polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Urine samples from 20 male workers in the polyester industry exposed by inhalation to styrene concentrations ranging from 29 to 41 ppm were investigated. Excretion products of styrene metabolism, mandelic acid and mercapturic acids, were purified from the urine over an extraction column packed with Porapak Q, with subsequent ether elution. The optical enantiomers R- and S-mandelic acid were then determined by thin layer chromatography (TLC) using chiral plate material and selective staining with vanadium pentoxide. Quantitative analysis of these compounds was performed using commercial reference substances. Styrene-specific mercapturic acids were analyzed by a modified TLC method, using synthesized reference substances. The concentration of racemic mandelic acid in the individual urine samples ranged from 80 to 1610 mg/l, and the ratio of the R- and S- enantiomers ranged from 0.7 to 2.2. These individual variations are not explained by differences in individual styrene exposure levels, or by differences in the concentration of the urine samples (in relation to creatinine excretion). Styrene-specific mercapturic acids were detected in the urine of only 1 of the 20 workers, at a concentration much lower than expected from previous investigations by others in humans and laboratory animals, in which less specific analytical methods had been used. The results point to marked interindividual differences in metabolism of styrene, probably related to enzyme polymorphisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050174
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  • 6
    Electronic Resource
    Electronic Resource
    Comparative genotyping and phenotyping of glutathione S-transferase GSTT1 (1996)
    Springer
    Archives of toxicology 70 (1996), S. 306-309 
    Details
    ISSN: 1432-0738
    Keywords: Key words Glutathione S-transferase GSTM1 GSTT1 ; Genotyping ; Phenotyping ; Epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Only limited information is available so far concerning the human glutathione S-transferase isoenzyme class theta encoded by the GSTT1 gene. The aim of the study was to characterize individuals in respect to a polymorphic deletion of the GSTT1 gene and to validate these results with the phenotypical determination of the “conjugator status” according to Hallier et al. (1993). Determination of the GSTT1 genotype was done in 40 healthy adults by using an assay based on internal standard controlled polymerase chain reaction. The GSTT1-1 phenotype was determined by measuring the erythrocyte conjugating activity towards methyl chloride using a gas chromatographic assay. Genotypically, 34 individuals out of 40 were classified as GSTT1 positive; the remainder were negative. These results could be confirmed by phenotyping in all but one case. In the present study the frequency of “non-conjugators” was 15%. Our study demonstrates the reliability of the suggested PCR assay for GSTT1 genotyping which is easier to perform than the phenotyping assay and is not affected by confounding factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050278
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  • 7
    Electronic Resource
    Electronic Resource
    Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder (1996)
    Springer
    Archives of toxicology 71 (1996), S. 123-126 
    Details
    ISSN: 1432-0738
    Keywords: Key words Glutathione S-transferase ; GSTM1 ; GSTT1 ; Bladder cancer ; Pharmacogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Onehundred-and-thirteen patients with cancer of the urinary bladder (cases) were examined with respect to the frequency of null genotypes of the polymorphic glutathione S-transferases GSTM1 and GSTT1. The allelic background in the German population of the area was evaluated by analysing 170 newborns (controls). The frequency of GSTM1 and GSTT1 null genotypes in this population, using methods based upon internal standard controlled polymerase chain reaction (PCR), was 0.54 and 0.18 respectively. An elevated relative bladder cancer risk of GSTM1 null genotype carriers was indicated by comparison of this background with the data of the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019). The frequencies of the GSTT1 null genotype in the total group of bladder cancer cases versus controls did not differ statistically. However, a significantly higher relative risk of bladder cancer for the GSTT1 null genotype was detected in the cases-subgroup of non-smokers (OR = 3.84; 95% CI [1.21, 12.23]; p = 0.023). Thus, the GSTT1 null genotype might represent a minor risk factor for human bladder cancer which should be further investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050366
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  • 8
    Electronic Resource
    Electronic Resource
    Preexistence of chronic tubular damage in cases of renal cell cancer after long and high exposure to trichloroethylene (1996)
    Springer
    Archives of toxicology 70 (1996), S. 259-260 
    Details
    ISSN: 1432-0738
    Keywords: Key words Trichloroethylene ; Renal cell cancer ; Tubular damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Substantially more cases of tubular damage were found among renal cell carcinoma patients who had been exposed to high levels of trichloroethylene over many years than among renal cell carcinoma patients who had not been exposed to trichloroethylene. This supports the hypothesis (Goeptar et al. 1995) that chronic tubular damage may be regarded as a necessary precondition for trichloroethylene to exert a nephrocarcinogenic effect. The findings also indicate that the urine protein patterns identified with SDS-PAGE may represent a valuable parameter for effect biomonitoring of persons exposed to high levels of trichloroethylene over many years.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050271
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  • 9
    Electronic Resource
    Electronic Resource
    Volume calibration of various gasmeters using a modified Tissot spirometer (1990)
    Springer
    European journal of applied physiology 61 (1990), S. 380-385 
    Details
    ISSN: 1439-6327
    Keywords: Calibration ; Tissot spirometer ; Kofranyi-Michaelis respirometer ; Wet gasmeter ; Oxylog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various methods for determinating energy expenditure by indirect calorimetry are used in laboratory and field studies such as the Douglas bag method, often used in combination with a wet gasmeter, the respirometer of Kofranyi and Michaelis (KM) and the Oxylog (OX). To calibrate the volume measurements of these pieces of apparatus a modified Tissot spirometer was built, consisting of an outer casing filled with water, a core and a bell. It was equipped with a solid counterbalance and with an additional roller chain, partly freely suspended on the side of the counterbalance. This construction allowed compensation for the varying buoyancies of the bell. The lift of the bell was measured by means of a vernier scale. From calculations of the geometric volume a revolution counter was adapted to record the moved volume in litres. By means of this spirometer volumes up to 2001 can be used for calibration at various physiological flow rates. Calibration procedures for KM, wet gasmeters and OX were developed. For OX a small inaccuracy up to 2.0% was observed within the flow range from 20 to 701·min−1. The inaccuracy increased at higher flow rates. Under defined calibration conditions the modified Tissot spirometer enabled repeated calibrations of different types of gasmeters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236056
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