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  • 1
    Electronic Resource
    Electronic Resource
    Influence of ethanol induction on the metabolic activation of genotoxic agents by isolated rat hepatocytes (1985)
    Springer
    Archives of toxicology 57 (1985), S. 217-221 
    Details
    ISSN: 1432-0738
    Keywords: Benzidine ; 2-Aminofluorene ; 2-Acetylaminofluorene ; Dimethylnitrosamine ; Diethylnitrosamine ; Isoniazid ; Cyclophosphamide ; Ethanol-induction ; Cytochrome P-450 ; N-acetylation ; Isolated rat hepatocytes ; Mutagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of ethanol-feeding to rats, over a 6-week period, on the activation of genotoxic compounds of different chemical classes, requiring metabolic conversion to exert their mutagenic activity, were studied in isolated rat hepatocytes. The influence of such treatment on cytochrome P-450 content and N-acetylation in isolated hepatocytes was also investigated. Benzidine (BZ), dimethylnitrosamine (DMN), diethylnitrosamine (DEN), isoniazid (INH) and cyclophosphamide (CP) were more effectively activated to products mutagenic towards Salmonella typhimurium by hepatocytes from ethanol-pretreated rats than by hepatocytes from controls. The mutagenic potency of 2-aminofluorene (2-AF) and 2-acetylaminofluorene (2-AAF) was not influenced by ethanol pretreatment. Ethanol consumption was found to be associated with increased cytochrome P-450 content and enhanced N-acetylation in the isolated hepatocytes. Our results support the hypothesis that an alteration of the hepatic drug-metabolizing system may be responsible for the ethanol-induced increase in susceptibility to certain genotoxic compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00324780
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of toluene and xylenes on liver glutathione and their urinary excretion as mercapturic acids in the rat (1980)
    Springer
    Archives of toxicology 43 (1980), S. 293-304 
    Details
    ISSN: 1432-0738
    Keywords: Toluene and Xylenes metabolism ; Glutathione ; Mercapturic acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of toluene and xylenes to rats caused a decrease in liver glutathione concentration. The effect was most pronounced after the administration of o-xylene. 26% of the initial glutathione level was found three hours after treatment with o-xylene (4.0 mmoles/kg). No in vitro conjugation of o-xylene with glutathione was observed, neither spontaneously nor in the presence of 105,000 g supernatant from rat liver homogenate, containing glutathione S-transferases. Thus, a metabolite of o-xylene, which is not formed during incubation with 105,000 g supernatant, reacts with glutathione. A thioether was isolated from urine of rats given o-xylene; the compound was identified as o-methylbenzyl mercapturic acid by GC-MS and NMR. Chromatographic evidence was found for the presence of benzyl mercapturic acid in the urine of toluene-treated rats. The amounts of mercapturic acids excreted in the urine after administration of toluene, p-xylene, m-xylene, and o-xylene were 0.4–0.7, 0.6, 1.3, and 10–21% of the dose, respectively. These results demonstrate the involvement of a thusfar unknown pathway in the biotransformation of toluene and xylenes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366185
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  • 3
    Electronic Resource
    Electronic Resource
    Beware of formaldehyde in disguise (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 373-375 
    Details
    ISSN: 1432-1041
    Keywords: formaldehyde ; methenamine ; health hazards ; carcinogenicity ; mutagenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The toxic potential of formaldehyde has recently been widely discussed, including the consequences of its release from certain building materials. The action of methenamine, used in the treatment of urinary infections, is based on the release of formaldehyde in the body. Various aspects of formaldehyde toxicity are discussed as a basis for reevaluation of methenamine and reconsideration of its safety.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613624
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  • 4
    Electronic Resource
    Electronic Resource
    Identification and determination of 2-thiothiazolidine-4-carboxylic acid in urine of workers exposed to carbon disulfide (1981)
    Springer
    Archives of toxicology 47 (1981), S. 51-58 
    Details
    ISSN: 1432-0738
    Keywords: Carbon disulfide ; Viscose rayon industry ; CS2-metabolite ; Biological monitoring ; 2-Thiothiazolidine-4-carboxylic acid ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A compound was isolated from the urine of workers exposed to carbon disulfide during the production of rayon. The compound was identified as 2-thiothiazolidine-4-carboxylic acid (TTCA) by GC/MS and NMR. A HPLC method for the quantitative determination of TTCA was elaborated and applied to urine samples. The method allowed detection of TTCA concentrations in urine as low as 5 × 10−7 M. No TTCA was detected in urine of workers occupationally exposed to organic solvents other than CS2. High concentrations of TTCA (upto 32×10−5 M) were shown to be present in urine of spinners exposed to CS2 concentrations of approximately 100 mg/m3. It is suggested that the assay of urinary TTCA is suitable for detection of occupational exposure to CS2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297130
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  • 5
    Electronic Resource
    Electronic Resource
    The interaction of chemical compounds with the functional state of the liver (1977)
    Springer
    International archives of occupational and environmental health 38 (1977), S. 197-207 
    Details
    ISSN: 1432-1246
    Keywords: Drug metabolizing enzymes ; Enzyme induction ; D-Glucuronic acid pathway ; D-Glucaric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Most of the enzymes which are involved in the biotransformation of chemical compounds are located in the liver. The activities of these enzymes can be altered by a great variety of foreign compounds. Especially lipophilic and relatively stable agents are capable of enhancing the activities of drug-metabolizing enzymes, after chronic exposure, by increasing the amount of these enzymes. Metabolism of foreign compounds generally results in the formation of much less toxic endproducts which can be excreted easily due to their more hydrophilic nature. However it is known that certain chemicals are converted to very toxic compounds which can produce various injuries. Enzyme inducers of course raise the possibility of impairments by accelerating the synthesis of these toxic metabolites. Numerous xenobiotic compounds are also capable of stimulating carbohydrate metabolism via the D-glucuronic acid pathway. In this pathway hexose is converted via UDPglucose, UDPglucuronic acid and D-glucuronic acid into D-glucaric acid, L-ascorbic acid and L-xylulose respectively. It has been demonstrated that at least in the case of short-term treatment a stimulation of the D-glucuronic acid pathway is based on an increased availability of UDPglucose in the liver cell which, in turn, is the result, of an inhibition of glycogen synthesis. Evaluation of the urinary excretion of D-glucaric acid as a reliable nonspecific test for diagnosing exposure to chemical compounds as well as the drug-metabolic capacity, will be the subject of the next article.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00378357
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  • 6
    Electronic Resource
    Electronic Resource
    The interaction of chemical compounds with the functional state of the liver (1977)
    Springer
    International archives of occupational and environmental health 38 (1977), S. 209-220 
    Details
    ISSN: 1432-1246
    Keywords: D-Glucaric acid ; Exposure test ; Biotransformation ; Enzyme induction ; Xenobiotic compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary At the present time, numerous chemicals are known to affect the activities of various hepatic enzymes, which find expression in an altered metabolism of both xenobiotic compounds and normal body constituents. A well-known example of the latter phenomenon is the stimulation of the D-glucuronic acid pathway resulting in an enhanced urinary excretion of D-glucaric acid. The results described in this study indicate that the urinary D-glucaric acid level is not necessarily related to the extent of the drug-metabolizing capacity of the liver. Experiments in which animals are treated with a large number of chemicals under different conditions demonstrate the usefulness of an altered D-glucaric acid excretion in urine as a nonspecific indicator for exposure to exogenous compounds. This conclusion is further supported by the results of investigations in which factory workers with exposure to different chemicals were tested for their urinary D-glucaric acid level. Alterations in the biotransformation of chemical compounds and the D-glucuronic acid pathway, caused by exogenous compounds, formed the subject of the first article.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00378358
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  • 7
    Electronic Resource
    Electronic Resource
    Detection and identification of S-methylcysteine in urine of workers exposed to methyl chloride (1980)
    Springer
    International archives of occupational and environmental health 46 (1980), S. 99-109 
    Details
    ISSN: 1432-1246
    Keywords: Methyl chloride ; Glutathione conjugation ; Thioethers ; Methylthio compounds ; Mercapturic acid ; S-methylcysteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Methyl chloride is used as a methylating agent and as a blowing agent in industrial processes. Alkylating agents and other electrophilic compounds are often detoxified in the organism through conjugation with glutathione. Glutathione conjugates are generally excreted as mercapturic acids, cysteine conjugates, or other thioethers in urine. Urine samples obtained from persons occupationally exposed to methyl chloride were examined for the presence of elevated thioether levels using a previously published non-selective procedure. No significant increases were detectable. A new assay procedure was developed for the detection of methylthio compounds in urine. The method is based on alkaline hydrolysis of urine samples and subsequent gas chromatographic determination of methyl mercaptan in the headspace of acidified hydrolysates. By application of this method a greatly increased excretion of a methylthio compound in the urine of CH3Cl-exposed workers was shown. The compound was identified as S-methylcysteine. A study of the urinary S-methylcysteine excretion in a group of workers during a seven-day shift revealed that two of six workers hardly excreted any S-methylcysteine after exposure to methyl chloride.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00378189
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  • 8
    Electronic Resource
    Electronic Resource
    Urinary mercapturic acid excretion as a biological parameter of exposure to alkylating agents (1977)
    Springer
    International archives of occupational and environmental health 39 (1977), S. 45-51 
    Details
    ISSN: 1432-1246
    Keywords: Mercapturic acid ; Biological alkylation ; Exposure of persons ; Thioether compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mercapturic acid derivatives or other thioethers can be considered as the endproducts of the metabolic detoxification of possibly alkylating agents. It is proposed that the appearance of these metabolites in the urine can be used as an indicator of exposure of the organism to such toxic compounds. A simple, practical procedure for determination of thioethers in urine samples is described. Employees of chemical and metal industries have been compared with respect to their urinary thioether concentrations. It was found that chemical workers excreted more thioether compounds than persons engaged in metal industry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381551
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  • 9
    Electronic Resource
    Electronic Resource
    Urinary cyclophosphamide assay as a method for biological monitoring of occupational exposure to cyclophosphamide (1986)
    Springer
    International archives of occupational and environmental health 58 (1986), S. 151-155 
    Details
    ISSN: 1432-1246
    Keywords: Cyclophosphamide ; Urine ; Hospital workers ; Biological monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Urine of twenty hospital workers was monitored for the excretion of the cytostatic drug cyclophosphamide using GC-MSD. The drug was found to be present above the detection limit of 0.5 μg/24 h urine in five cases. A clear relationship between cyclophosphamide handling and the detectability of excretion existed. This method developed can be of use for biological monitoring studies directed toward the finding of exposure hazards.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00380766
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  • 10
    Electronic Resource
    Electronic Resource
    Thioether concentration and mutagenicity of urine from cigarette smokers (1979)
    Springer
    International archives of occupational and environmental health 43 (1979), S. 159-166 
    Details
    ISSN: 1432-1246
    Keywords: Urinary thioethers ; Mercapturic acids ; Mutagenicity of urine ; Cigarette smoking ; Potentially alkylating agents ; Exposure test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Urinary thioether compounds, such as mercapturic acids, can be considered as nontoxic end products of potentially alkylating agents. On the other hand, urinary mutagenicity may represent the excretion of potential mutagens that have not definitively been detoxified by the organism. It is suggested that a combined urinary thioether and mutagenicity test may be useful in monitoring people occupationally exposed to potentially alkylating compounds, in particular to mixtures of these chemicals. Exposure to cigarette smoke, containing several known mutagens and carcinogens, is expected to interfere with the test results. The excretion of mutagens and thioethers was determined in urine of smokers and nonsmokers. Smokers excrete more mutagens and thioether compounds than nonsmokers. Further, it was found that the urinary mutagenicity and thioether level are significantly related to the amount of cigarettes smoked.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381187
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