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Biomedical subjects

M Metzler

Publications and source records attributed to M Metzler.

At least 145 records · Page 8Linked to original sources
PubMed1980

Identification of potential carcinogens in technical grade 1,1,1-trichloroethane.

Gas chromatography and gas chromatography-mass spectrometry were employed to analyze 22 samples of technical grade 1,1,1-trichloroethane for impurities. Eighteen contained vinylidene chloride (1,1-dichloroethylene) (30-900 micrograms/ml) and further contaminants were identified as 1,1-dichloroethane (11), trichloroethylene (12), and 1,1,2-trichloroethane (9). Nitromethane (18), 1,2-epoxybutane (19), tert. butanol (7), and dioxane (10) were detected as stabilizers. It is recommended that the manufacturers should eliminate vinylidene chloride and stabilizers which carry a carcinogenic and/or mutagenic risk, from technical samples of 1,1,1-trichloroethane.

Animals↗
PubMed1980

Peroxidase activity in the rat Zymbal gland and its possible role in the metabolic activation of aminostilbenes in the target tissue.

Peroxidase (EC 1.11.1.7) activity is detected in the rat Zymbal gland, which is the target organ of trans-4-dimethylaminostilbene (trans-DAS) carcinogenicity. Measurements of peroxidase activity in ovariectomized rats show that the enzyme activity is lowered in the uterus and Zymbal gland by trans-DAS treatment and in the lungs by diethylstilboestrol (DES) treatment. In an in vitro system containing horseradish peroxidase (HRP), hydrogen peroxide and calf-thymus DNA, irreversible binding of the 3H-labelled trans-DAS metabolites 3-hydroxy-, 4'-hydroxy-, and N-hydroxy-4-acetylaminostilbene to DNA is observed. The peroxidase activity in the Zymbal gland together with the HRP-catalyzed oxidation of trans-DAS metabolites suggest a possible role for peroxidase in the organ-specific metabolic activation of trans-DAS.

Animals↗
PubMed1980

Metabolic fate of diethylstilbestrol in the Syrian golden hamster, a susceptible species for diethylstilbestrol carcinogenicity.

1. Diethylstilbestrol, after oral administration to Syrian golden hamsters, is preferentially excreted in the faeces in males, and in about equal amounts in urine and faeces in females. Glucuronides comprise the major urinary conjugate for both sexes. 2. Eleven oxidative metabolites of diethylstilbestrol have been identified in the urinary glucoronide fraction. They represent aliphatic hydroxy-, aromatic hydroxy-, and aromatic methoxy-derivatives of diethylstilbestrol, pseudo diethylstilbestrol, and dienestrol. 3. No sex difference in the oxidative metabolism of diethylstilbestrol was observed in the hamster. 4. Detailed chromatographic and mass spectrometric information on the various metabolites is provided and discussed.

Animals↗
PubMed1980

Noninvasive determination of LeVeen shunt patency.

The LeVeen peritoneovenous shunt is being used with increasing frequency for management of intractable ascites. The question of postoperative shunt patency frequently arises. This report describes a unique, noninvasive method of assessing shunt patency using Doppler ultrasound. Four of five patients with shunts judged to be occluded by this new method had the findings substantiated by peritoneal instillation of radioisotope; the fifth patient was not studied by any other method. The evaluation with ultrasound is easily performed at operation and after operation and is reliable for assessing shunt patency.

Ascites↗
PubMed1980

Decomposition of the neuro- and nephrotoxic compound dichloroacetylene in the presence of oxygen: separation and identification of novel products.

Dichloroacetylene (DCA) shows pronounced nephrotoxic effects in several animal species and is neurotoxic in humans. It is a chemically highly reactive compound that decomposes spontaneously in the presence of oxygen. The chemical decomposition of DCA has been studied in order to understand the role of the decomposition products for the toxic effects of DCA. Seven compounds were identified by their mass spectra and by comparison with authentic reference materials. Among these were phosgene, hexachlorobutadiene, and other reactive products (e.g., trichloroacetyl chloride and trichloroacryloyl chloride), which may explain, in part, the toxicity of DCA.

Acetylene↗
PubMed1979

Metabolites of diethylstilboestrol induce sister chromatid exchange in human cultured fibroblasts.

Diethylstilboesterol (DES) is one of the few substances for which a clear association with carcinogenicity has been established in man. Nevertheless, it is still widely used, mainly as a cheap oestrogen to increase the slaughter weight of beef, but in spite of this it is not known if residues in the meat or metabolites excreted by the cattle are hazardous to man. It is also unknown whether there is a threshold dose below which DES is harmless. A threshold might be expected if a hormonal mechanism of carcinogensis rather than metabolic activation to an electrophically reactive species operats. This possibility was supported by the observations that DES, in contrast to most other carcinogens, failed to induce mutations in the Salmonella/microsome test or malignant transformations of eukaryotic cells in culture. It is also disturbing that DES, one of the few known human carcinogens was negative in these two most widely used short-term tests introduced as fast early-earning system for potential carcinogens. We now report that DES is positive in sister chromatid exchange (SCE) induction, a short-term test for which a high correlation with the carcinogenicity of the compounds tested has been observed. Moreover, we show that metabolic activation was involved. Two different pathways leading to metabolites much more active in SCE induction than DES itself ('proximate agents') were established.

Cells, Cultured↗
PubMed1979

Molecular mechanism of 1,1-dichloroethylene toxicity: excreted metabolites reveal different pathways of reactive intermediates.

The excretion and biotransformation of [14C] 1,1-dichloroethylene (vinylidene chloride, VDC) after administration of a single oral dose has been investigated in female rats. Seventy-two hours after a dose of 0.5, 5.0, and 50.0 mg/kg, 1.26, 9.70, 16.47%, respectively, are exhaled as unchanged VDC, and 13.64, 11.35, 6.13% as 14CO2. The main pathway of elimination is through renal excretion with 43.55, 53.88, 42.11% of the administered radioactivity. Through the biliary system, 15.74, 14.54, 7.65% of the activity are eliminated. The isolation of the main metabolites of VDC from 24 h urine is accomplished through the combined application of solvent extraction, ion exchange chromatography and thin layer chromatography. Then gas chromatography and mass spectrometry are used for their identification. Three metabolites have been identified: thiodiglycolic acid, N-acetyl-S-(2-carboxymethyl)cysteine and methyl-thio-acetylaminoethanol. In addition, three smaller unidentified radioactive peaks have been found. Thiodiglycolic acid is the main metabolite in VDC metabolism. The simultaneous formation of an ethanolamine- and a cysteine-conjugation product points to different reaction pathways of the postulated intermediate reactive epoxide; ethanolamine probably originates from membrane lipids, which react with VDC-epoxide and/or its derivatives. This pathway could explain, in part, the parenchyma damaging effect of VDC.

Administration, Oral↗
PubMed1979

Diethylstilbestrol metabolic transformation in relation to organ specific tumor manifestation.

Oxidative biotransformation of the synthetic estrogen diethylstilbestrol (DES) gives rise to several reactive compounds. Two mechanisms are proposed concerning the possible involvement of reactive metabolites in the organotropic tumorigenesis of DES. The first mechanism suggests an affinity of the metabolite to the estradiol receptor present in estrogen target organs. This has been shown for the olefinic epoxide of DES. The second mechanism is based on the organ specific oxidation of DES by peroxidase. The intermediates of this reaction were found to bind to nucleic acid and protein in a manner characteristic of chemical carcinogens.

Animals↗
PubMed1979

A novel fluorinated derivative of diethylstilbestrol.

The synthesis of the diethylstilbestrol (DES) derivative with fluorine atoms present in the positions ortho to the hydroxyl in each ring is described. In vitro studies in a system containing horse radish peroxidase/H2O2 demonstrate extensive oxidation of tetrafluorodiethylstilbestrol to the corresponding dienestrol derivative. Tetrafluorodiethylstilbestrol and DES had comparable in vivo uterotropic activities at a dose of 100 microgram/kg. Competitive binding experiments demonstrated 20-25 fold reduced interaction with the mouse uterine estrogen receptor. This compound may be useful as an experimental estrogen in distinguishing between the biological and toxic effects of DES.

Animals↗
PubMed1979

Diethylstilbestrol and 11 derivatives: a mutagenicity study with Salmonella typhimurium.

Diethylstilbestrol was tested for mutagenicity with his- S. typhimurium strains under 10 different matabolic situations (no exogenous metabolizing system; S9 mix from liver homogenate of rats induced with Aroclor 1254, with or without inhibition of epoxide hydratase; liver and/or kidney S9 mix from control or hamsters treated with Aroclor 1254; horse-radish peroxidase + H2O2). Under none of these conditions did diethylstilbestrol give any indication of a mutagenic effect. Furthermore, 11 metabolites and other derivatives of diethylstilbestrol, 2 of them potent inducers of sister-chromatid exchange in cultured fibroblasts, were not mutagenic with any of the 4 tester strains (S. typhimurium TA100, TA98, TA1537, TA1535) in the presence or absence of S9 mix from liver homogenate of rats induced with Aroclor 1254. Thus, one of the few known human carcinogens is very resistant to detection by the mammalian enzyme-mediated Salmonella typhimurium mutagenicity test (Ames test). This is especially remarkable since the metabolizing systems used included: (1) some of very high metabolic activity (S9 mix from liver homogenate of rats and hamsters induced with Aroclor 1254); (2) metabolizing systems from organs susceptible to the carcinogenic activity of diethylstilbestrol (hamster kidney); as well as (3) a mixture of (1) and (2) in case both activities are required for the carcinogenic effect in the whole animal.

Diethylstilbestrol↗
PubMed1979

Vasospastic disorders.

Acute digital ischemia not due to thromboembolism may be the result of either a primary vasospastic disorder (Raynaud's disease, acrocyanosis, livedo reticularis) or vasospasm associated with a systemic, regional, or traumatic disorder (Raynaud's syndrome, cold injury). Raynaud's disease versus syndrome is distinguishable up to 95% of the time from clinical criteria.

Arteries↗
PubMed1979

Diethylstilbestrol: evidence for metabolic activation in man, rat, and hamster.

Oxidative biotransformation of radioactively and deuterium-labeled DES gives rise to several metabolites in intact Wistar rats, Syrian golden hamsters, and humans. With the use of radio gas chromatography and gas chromatography--mass spectrometry, the major urinary and biliary metabolites were tentatively identified as hydroxy and methoxy derivatives of DES and dienestrol, of which the relative amounts excreted depended largely on the species. Some of the metabolites are potentially reactive substances or have reactive metabolic precursors such as epoxides or allylic hydroxy compounds that might be associated with the adverse effects of DES.

Adult↗