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Biomedical subjects

H Schwind

Publications and source records attributed to H Schwind.

7 recordsLinked to original sources
PubMed1979

Mutagenicity of 43 structurally related heterocyclic compounds and its relationship to their carcinogenicity.

43 heteropolycyclic compounds belonging to a homologous series were investigated for mutagenicity. The results are compared with carcinogenicity data obtained with the same batches of compounds under conditions identical for all of them. Mutagenicity was tested in the Ames test with Salmonella typhimurium strains TA1535, TA1537 and TA100 in the presence and absence of liver 10 000 g supernatant from rats treated with Aroclor 1254. Carcinogenicity was tested by injection of the compounds into subcutaneous tissue of XVIInc/Z mice. 18 test compounds showed carcinogenic activity, some strongly, others only weakly. Of these, 17 were detected as mutagens: one weak carcinogen did not revert the Salmonella strains. No quantitative correlation was observed between the extents of the mutagenic and the carcinogenic effects. Of the 25 substances that did not produce tumours, 13 showed mutagenicity (12 in the presence, 2 in the absence, of the liver homogenate). The mutagenic effects of these compounds were quantitatively similar to those of the compounds that produced tumours. The most sensitive strain of Salmonella typhimurium was TA100. It detected all 30 mutagens. TA98 was mutated by 25 compounds, TA1537 by 16 compounds. No mutagenic effects were seen with TA1535. Possible reasons for the high percentage of apparently "false positives" in the Ames test and the lack of a quantitative correlation between the potency of the mutagenic and carcinogenic effects are discussed. It is suggested that the complexity of the metabolism of these heterocyclic compounds may lead to critical differences in metabolism in mouse subcutaneous tissue in vivo and in liver homogenates from rats treated with Aroclor. Therefore the present study will be extended to life-long oral and intrahepatic carcinogenicity tests leading to a higher proportion of metabolism in the liver.

Carcinogens↗
PubMed1978

[Gas chromatographic determination of di- and trisaccharides (author's transl)].

Three new methods are reported for the gas chromatographic analysis of di- and trisaccharides. Method I: Sugars are converted into their methoximes by reaction with methoxylamine hydrochloride in pyridine, followed by esterification with acetic anhydride. The separation is performed on OV 225 at 260 degrees C. Method II: Disaccharides are reduced to the alditols with sodium borohydride in aqueous solution, followed by acetylation with acetic anhydride in pyridine. In this method, only one peak is observed for each sugar. The derivatives are separated on OV 225 at 260 degrees C. Method III: Sugars are converted into their methoximes by reaction with methoxylamine hydrochloride in pyridine, followed by trifluoroacetylation with N-methyl-bis (trifluoroacetamide). The trisaccharide derivatives still show sufficient volatility. The separation is performed on OV 101 at 130 degrees C for disaccharides, and at 160 degrees C for trisaccharides. The retention times for biologically occurring di- and trisaccharides such as maltose, maltotriose, lactose, and sucrose are reported. The reliability criteria for method I are reported for the analysis of lactose, maltose and sucrose.

Chromatography, Gas↗
PubMed1977

Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites.

Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide hydratase and monooxygenases are reflected in very dramatic differences in mutagenicity of benzo(a)pyrene which varied from extremely potent to a degree which could easily be overlooked. In order to investigate whether the differences in enzyme activities were causally linked to the observed differences in mutagenicity, the enzyme activities were modulated by inhibition and induction. These manipulations were always accompanied by the corresponding changes in mutagenicity. It is concluded that species such as mice which possess high monooxygenase activity but very low epoxide hydratase activity are much more susceptible than man to those toxic effects which are mediated by metabolically formed epoxides which are substrates of epoxide hydratase. In this regard, it is especially noteworthy that mice possess a much lower hepatic epoxide hydratase activity than man.

Animals↗