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H G Neumann

Publications and source records attributed to H G Neumann.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biological monitoring of 1,3-butadiene: species differences in haemoglobin binding in rat and mouse.

The adduct formed by the reaction of 1,3-butadiene monoxide, a major metabolite of the mutagen and carcinogen 1,3-butadiene, with the N-terminal valine of haemoglobin was used as a dosimeter for the bioavailability of reactive metabolites. The dose-dependence of adduct formation was studied in female CB6F1 mice and female Wistar rats exposed to 0, 50, 200, 500 or 1300 ppm butadiene in an open inhalation chamber for 6 h per day for five consecutive days. Globin was isolated 18 h after the last exposure, and N-terminal valine was obtained by a modified Edman degradation procedure. Adduct levels were five times higher in mice than in rats (17 and 3.5 nmol/g globin, respectively, at 500 ppm), which may partially explain the greater susceptibility of mice to tumour formation. Adduct levels increased linearly with dose in rats, whereas in mice this slope of the curve became flatter at 500 ppm and increased with higher doses. Similar results were obtained in male and female C3H x 101/EL mice.

Administration, Inhalation↗
PubMed1990

Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners.

Covalent binding of benzidine and some congeners to hemoglobin was studied in female Wistar rats after oral administration. Hemoglobin adducts were hydrolyzed under alkaline conditions, and the arylamines extracted and analysed by HPLC with electrochemical detector. With benzidine, three cleavage products were observed, the major component being monoacetylbenzidine. This indicates that 4-nitroso-4'-N-acetylaminobiphenyl is the major reactive metabolite in erythrocytes. In addition benzidine and 4-aminobiphenyl were identified. The latter indicates a hitherto unknown metabolic pathway of benzidine. With 3,3'-dichlorobenzidine-dihydrochloride, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine two cleavage products were observed, the parent diamines being present in excess to or in amounts comparable to the monoacetyl derivative. With 3,3',5,5'-tetramethylbenzidine a hemoglobin adduct could not be found. When the azo dye direct red 28 was administered to the animals, the three cleavage products typical for benzidine were found, indicating that benzidine became bioavailable after reductive cleavage of the azo compound. In this case the fraction of 4-aminobiphenyl was greater than after benzidine. It is proposed to use the analysis of hemoglobin adducts in human blood to control the exposure of individuals to these carcinogenic chemicals in the course of biochemical effect monitoring.

Administration, Oral↗
PubMed1990

Quantification of haemoglobin binding of 4,4'-methylenebis(2-chloroaniline) (MOCA) in rats.

4,4'-Methylenebis(2-chloroaniline) (MOCA) is used as a curing agent in the production of polyurethane. MOCA is carcinogenic in experimental animals. Haemoglobin adducts have been proposed as dosimeters of aromatic amines for biological monitoring. A quantitative method to determine the adduct has now been worked out in female Wistar rats dosed per os with 3.82, 14.2 and 16.2 mumol/kg 14C-ring labeled MOCA or 0.25 and 0.50 mmol/kg unlabeled MOCA. MOCA bound in decreasing amounts to DNA, RNA and proteins of the lung, liver and kidney. Fractions of 0.19% and 0.026% of the dose were bound to the blood proteins haemoglobin and albumin, respectively. MOCA released by hydrolysis from haemoglobin was determined by HPLC with electrochemical detection or by GC-MS. Albumin did not form any hydrolysable adducts with MOCA.

Animals↗
PubMed1990

The tentative identification of DNA-adducts generated by trans-4-dimethylaminostilbene and trans-4-acetylaminostilbene in rats.

Tritium-labeled trans-4-dimethylaminostilbene (DAS) and trans-4-acetylaminostilbene (AAS) were administered orally to female Wistar rats. RNA and DNA were isolated from livers after 24 h and 28 days. Hydrolysates were analyzed by gel filtration and HPLC. Total binding to nucleic acids and elution profiles of hydrolysates were very similar for both aminostilbene derivatives. The large polar fraction eluting early in Sephadex LH20 chromatograms accounting for 60-80% of total DNA-bound radioactivity could not be assigned to individual base adducts and most likely is not due to incomplete hydrolysis but rather to cross-links between bases or proteins and bases. Of the total radioactivity bound to nucleic acids 6-7% in RNA and 3-5% in DNA could be tentatively identified as four isomeric, cyclic guanine adducts (predominantly (S,S)- and (R,R)-guanine-N2,beta-N3,alpha-N-acetylaminobibenzyl) by cochromatography with synthetic reference compounds. The most abundant single adduct accounting for 20-30% of RNA-bound radioactivity (fraction G in Sephadex LH20 chromatography) could not be identified. The long-term experiment revealed different persistence of DNA adducts: the polar material decreased to about 2/3, the cyclic guanine adducts (fraction d-B) to about 1/3 to 1/2 within 4 weeks, whereas one of the unidentified DNA-adducts (fraction d-E) persisted completely. AAS labeled in the acetyl group was administered in an additional experiment. The presence of the acetyl group could be demonstrated in most of the adducts, but non-acetylated adducts were found also. The ratio of non-acetylated:acetylated cyclic B-adducts in RNA was 1:2 from DAS and 1:13 from AAS, in DNA 1:3 and 1:10, respectively.

Animals↗
PubMed1990

Biomonitoring of arylamines: hemoglobin adducts of urea and carbamate pesticides.

Hemoglobin adducts of aromatic amines released from pesticides were investigated. Female Wistar rats were dosed orally with pesticides up to 1 mmol/kg body weight. Blood was obtained after 24 h, hemoglobin isolated and hydrolyzed in 1 NaOH. The amines were extracted and quantified by gas chromatography with nitrogen-specific or mass-selective detection. The following binding indices [HBI, hemoglobin binding index = binding (mmol/mol Hb) per dose (mmol/kg)] were obtained: pesticide (arylamine): linuron, diuron (3,4-dichloroaniline) 0.8 and 4.5 respectively; monuron, monolinuron (4-chloroaniline) 39 and 55 respectively; chlorpropham (3-chloroaniline) 2.9; chlordimeform (4-chloro-o-toluidine) 2.4; propham (aniline) 2.4. With vinclozoline and iprodione (3,5-dichloroaniline) and quintozene (pentachloroaniline) no adducts could be found. The results demonstrate the possible use of arylamine-hemoglobin adducts for measuring the bioavailability of potentially hazardous components of pesticides and the extent to which they are formed and metabolically activated.

Animals↗
PubMed1990

Competitive binding affinity of carcinogenic aromatic amines to the rat hepatic aromatic hydrocarbon (Ah) receptor in vitro and potency to induce monooxygenase activity in vivo.

The aromatic amides 2-acetylaminofluorene (2-AAF), its isomer 4-acetylaminofluorene, 2-acetylaminophenanthrene (AAP), trans-4-acetylaminostilbene (AAS) and the corresponding amines differ in their carcinogenic effects in the rat. Only 2-AAF and 2-aminofluorene (2-AF) are tumor promoters in rat liver. We have determined the competitive binding affinities of these compounds to the rat hepatic cytosolic aromatic hydrocarbon (Ah) receptor, which has been associated with tumor promotion. Binding affinity was determined by displacement of labelled 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) or 3-methylcholanthrene. The rank order of affinities and the apparent inhibitor constants measured with the sucrose density gradient centrifugation technique were: AAF (2.3 microM) greater than AAP (2.7 microM) greater than 2-AF (7.0 microM) greater than trans-4-aminostilbene (7.7 microM) greater than 2-aminophen-anthrene (10.4 microM). 4-Acetylaminofluorene, 4-aminofluorene and AAS did not displace TCDD from the receptor protein. A number of other fluorene derivatives did not bind, except 2-nitrofluorene (apparent inhibitor constant (1.4 microM). The in vivo biological potency of the aromatic amines was monitored by measuring the induction of ethoxy-resorufin-O-deethylase (EROD) and aromatic hydrocarbon hydroxylase activities. In vitro binding to the Ah receptor correlates roughly with the induction of EROD activity. The effect of 2-AAF was dose dependent, supporting a receptor-mediated mechanism. The correlation between Ah receptor affinity and tumor-promoting properties of the tested aromatic amines is only limited, but the results are not at variance with the concept of a receptor-mediated process in 2-AAF tumor promotion.

2-Acetylaminofluorene↗
PubMed1990

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

It has been demonstrated in several model systems that tumors arise in a multistage process. Carcinogenic aromatic amines are complete carcinogens, which usually produce tumors in typical target tissues without any additional treatment. The tissue specificity, however, cannot readily be explained by genotoxic effects, and the role of secondary effects is not well understood. Promotional pressure on initiated cells can be produced by endogenous factors but also by the chemical itself. Comparison of the effects on rat liver of 2-acetylaminofluorene (AAF) and trans-4-acetylaminostilbene (AAS) provides some evidence that initiating and promoting properties of these chemicals can be separated. AAS is a strong initiator in rat liver but seems to lack promoting activity; AAF is a less efficient initiator but has tumor promoting properties. The results obtained so far indicate that promoting pressure is not produced by the acute, cytotoxic effects of AAF. It is therefore concluded that nongenotoxic, possibly receptor-mediated effects are involved.

2-Acetylaminofluorene↗
PubMed1989

[The incidence of borderline and pathologic findings in young females within the scope of gynecologic-cytologic screening studies].

The frequency of Pap III-V findings in cytological screening examinations in Rostock-City was estimated for the age groups 16-20, 21-25 and 26-30 years. Two 3-year periods (1972-1974 and 1981-1983) were compared. A significant 9-fold increase of cytological results of Pap groups III-V was found during this time. Possible causes of this changing pattern, especially papillomavirus infections were discussed. In the age group 26-30 years there was the highest progression rate with almost 10%, in contrast to 1% in the age group 16-20 years. In the three investigated age groups a regression rate of 46% and a persistence rate of 38% were found. The results underline the increasing importance of gynecocytological screening examinations in young women.

Adolescent↗
PubMed1988

Biomonitoring of aromatic amines and alkylating agents by measuring hemoglobin adducts.

Analysis of hemoglobin adducts in blood samples is suitable for the biological monitoring of genotoxic chemicals. The method is specific because the compound to which the individual was exposed is identified. The sensitivity of the method depends on the analytical procedure applied, but is hardly limiting since large amounts of the protein can be obtained. The method provides not only information about the internal exposure to the environmental chemical, but also about the individual's capacity to generate ultimate genotoxic metabolites from it. Since macromolecular damage in blood cells is correlated to that in potential target tissues, this information is relevant to risk assessment, insofar as macromolecular damage produced by a specific chemical can be correlated with the development of tumors.

Alkylating Agents↗
PubMed1988

Biomonitoring of aromatic amines II: Hemoglobin binding of some monocyclic aromatic amines.

Covalent binding of 13 monocyclic aromatic amines to hemoglobin was studied in female Wistar rats and hemoglobin binding indices were determined. The hemoglobin adducts were hydrolyzed under alkaline conditions. In all cases the parent amine could be identified by gas chromatography and with one exception represented the only cleavage product. The binding index varied considerably and was highest with p-chloroaniline (569) and lowest with 2,4,5-trimethylaniline (0.7). Five compounds were also studied in female B6C3F1 mice. Hemoglobin binding was lower than in rats, but to varying degrees. Hemoglobin binding correlated remarkably well with the maximum methemoglobin level achieved with the six examples studied. The results support the notion that the reaction of nitrosoarenes, as metabolites of arylamines, with hemoglobin represents a general pathway in vivo. The analysis of such hemoglobin adducts is recommended as a dosimeter in biological monitoring of humans in order to control exposure. It is too early, however, to assess the carcinogenic risk from hemoglobin binding data with these compounds.

Amines↗