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Biomedical subjects

H G Neumann

Publications and source records attributed to H G Neumann.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Induction of single-strand breaks and interstrand cross-links in liver DNA after the administration of 2-acetylaminofluorene and trans-4-acetylaminostilbene to rats.

2-Acetylaminofluorene (AAF) or trans-4-acetylaminostilbene (AAS) was orally or intraperitoneally administered to female Wistar rats. DNA from liver cells was analyzed for single-strand breaks by the alkaline elution assay. Only borderline effects were observed with doses (100 mumol/kg) used in animal carcinogenesis experiments. Even high doses of AAF (1,000 mumol/kg) were not effective. Methyl methanesulfonate (MMS) in vivo and gamma irradiation in vitro were shown to produce dose-dependent DNA single-strand breaks (positive control). Only a marginal effect was obtained with 100 mumol/kg MMS. The elution rate of DNA was increased by a factor of 34 in liver cells in vitro with 400 rad of gamma irradiation. Only a fraction of this rate could be demonstrated immediately after irradiation in vivo, and no lesions were found two hours later. This strongly indicates the rapid repair of single-strand breaks. Additional experiments showed that AAS, a nonhepatocarcinogen, produced more interstrand cross-links in the rat liver DNA than did AAF.

2-Acetylaminofluorene↗
PubMedDate not supplied

Biomonitoring of aromatic amines V: acetylation and deacetylation in the metabolic activation of aromatic amines as determined by haemoglobin binding.

Aromatic amines are metabolically activated by N-oxidation of either the amine or the acetamide as a first step and esterification of the resulting N-hydroxyl derivatives as a second step. Both pathways may lead to DNA-adducts and subsequently to DNA lesions and mutations. Since the accumulation of non-acetylated adducts has been associated with tumour initiating properties, the balance between acetylation and deacetylation may greatly influence the biological effect. Hydrolysable haemoglobin adducts representing the bioavailability of N-hydroxylamines and the corresponding nitroso-derivatives were analysed following oral administration to female Wistar rats of two arylamine-acetamide couples: 4-aminobiphenyl and 2-aminofluorene, and two arylamine-acetamide-diacetamide triples: benzidine and 3,3'-dichlorobenzidine. The results show that the monoacetamides are readily deacetylated in vivo whereas the diacetamides are not. A dynamic equilibrium is indicated to exist between acetylation and deacetylation, which depends on substrate specificity, and the role of deacetylation is emphasised. In addition, acetylation polymorphism was studied with 4-chloroaniline and 3,3'-dichlorobenzidine in slow acetylating A/J and rapid acetylating C57BL/6J mice. The slow acetylator genotype was associated with significantly higher haemoglobin-adduct levels for both arylamines. The results provide additional support for the use of haemoglobin adducts in biomonitoring as a dosimeter for the biologically active dose of arylamines/arylacetamides. Moreover, biomonitoring of haemoglobin adducts may provide information about an individual's susceptibility to the toxic and carcinogenic effects of these chemicals.

Acetylation↗
PubMedDate not supplied

Health risk of combustion products: toxicological considerations.

Combustion of organic material produces an almost uncountable number of products among which are many chemicals known to have toxic properties. A pertinent example is the diesel engine emission. There is concern about the possible health effects and we would like to know what risk is associated with the exposure. If risk is defined as the probability that a certain health effect occurs within a defined time span or as a result of a certain strain (Royal Society Study Group)--and it is important to emphasize the quantitative aspect of this definition--we must admit that we do not know a good answer. The example of diesel exhaust is used to demonstrate the toxicological approach to risk characterization in general and the possible improvement of exposure assessment with nitroarenes as indicators for environmental contaminations in particular.

Air Pollutants↗
PubMedDate not supplied

Toxic equivalence factors, problems and limitations.

It is a particular problem to set tolerance levels for mixtures containing chemicals classified as carcinogens. In the case of chlorinated dioxin and furan congeners, 'toxicity equivalence factors' (TEFs) were introduced. This concept has problems in itself and cannot be readily transferred to other mixtures, such as those of monocyclic nitroarenes in wastes of trinitrotoluene (TNT)-based explosives. The difficulties in finding suitable endpoints to compare the components are discussed (methaemoglobin formation; quantitative structure-activity relationships; mutagenicity; carcinogenicity). An alternative approach for the development tolerance levels in this instance is based on results obtained by measuring haemoglobin adducts as biomarkers of the most prevalent mixture components in humans.

Animals↗
PubMedDate not supplied

Reaction of arylnitroso compounds with mercaptans.

1. The non-enzymic reactions of trans-4-nitrosostilbene, 4-nitrosobibenzyl, 2-nitrosofluorene and p-nitrosotoluene with glutathione were studied. 2. Three types of reaction products have been identified, namely, the corresponding hydroxylamine, amine, and a water-soluble adduct which hydrolyses under acidic or alkaline conditions to an amine and glutathione sulphinic acid. 3. Reduction to the amine is explained by formation of adducts which are reduced by glutathione with the production of oxidized glutathione. 4. The relevance of this reaction for metabolic activation and inactivation of aromatic amines in vivo is discussed.

Bibenzyls↗
PubMedDate not supplied

Modulation of trans-4-acetylaminostilbene metabolism in the rat by methylcholanthrene and phenobarbital and its relevance for acute toxicity.

trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic to rats. Animals can be protected from the effects of a lethal dose by pretreatment with methylcholanthrene (MC), but not with phenobarbital (PB). In order to study the effects of these pretreatments on pharmacokinetic parameters, single, acute toxic doses of 3H-trans-AAS were orally administered to female Wistar rats and metabolism and excretion studied in untreated and PB- and MC-pretreated animals. MC pretreatment enhanced the rate of metabolism and the excretion of metabolites into the bile, but did not alter urinary excretion. After 3 days, 46, 86, and 52% of the administered dose was excreted, respectively, in untreated, MC-pretreated, and PB-pretreated animals. MC pretreatment modified both phase I and phase II metabolism of trans-AAS. Urinary excretion of unconjugated metabolites was decreased accompanied by an increased formation of sulfates. Biliary excretion of glucuronides and conjugated polar metabolites was increased by MC pretreatment. It is concluded that MC protects rats from acute trans-AAS toxicity by increasing the rate of total metabolism and enhancing metabolic (conjugation) pathways of inactivation relative to putative activation by oxidative metabolism.

Animals↗