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Biomedical subjects

H Bartsch

Publications and source records attributed to H Bartsch.

At least 325 records · Page 18Linked to original sources
PubMed1987

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants in high- and low-risk areas for stomach cancer in northern Japan.

Three samples of 24-h urine were collected from each of 104 inhabitants of high-risk (Akita) and low-risk (Iwate) areas for stomach cancer in northern Japan, according to the following protocols: (i) when they were undosed, (ii) after ingestion of proline three times a day and (iii) after ingestion of proline together with vitamin C three times a day. These samples were analysed for N-nitrosamino acids, nitrate and chloride ion as indices of the exposure. The median values of N-nitrosoproline (NPRO) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA) excreted in the urine of undosed subjects were not different between the two areas; however, that of N-nitrosothiazolidine 4-carboxylic acid (NTCA) was significantly higher in subjects of the high-risk area. Salt intake, estimated from the level of chloride ion in the urine, did not differ in two areas. After intake of proline, the NPRO level increased significantly only in subjects of the high-risk area, but not in those of the low-risk area; intake of vitamin C inhibited this increase of NPRO and lowered the levels of other nitrosamino acids only in the high-risk subjects. In contrast, the urinary level of nitrate was higher in subjects of the low-risk area than in those of the high-risk area; nitrate levels were found to correlate well with the amounts of vegetables consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗
PubMed1987

A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.

Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.

Adult↗
PubMed1986

Trapping of chemical carcinogens with magnetic polyethyleneimine microcapsules: I. Microcapsule preparation and in vitro reactivity of encapsulated nucleophiles.

In this paper we describe the synthesis and characterization of magnetic microcapsules, intended for use in vivo, and which contain polyethyleneimine nucleophilic targets capable of trapping electrophilic carcinogens. The microcapsules, 15-50 microns in diameter, consist of a semipermeable cross-linked nylon membrane surrounding core polyethyleneimine and magnetite. These microcapsules can be readily manipulated and extracted from aqueous suspensions by magnetic fields. Core polyethyleneimine was released after membrane rupture by sonication. Magnetic hemoglobin microcapsules were also prepared but were unsuitable due to precipitation of hemoglobin within the core. Treatment by proteolytic enzymes that are present in the gastrointestinal tract caused microcapsule damage resulting in protein release, whereas polyethyleneimine microcapsules remained unaffected. After incubation with N-[methyl-14C]-N-nitrosourea, (1) the microcapsules retained covalently bound radiolabel, both in core polyethyleneimine and the microcapsule membrane. The efficiency of the binding of 1 was investigated by varying the polymer concentration during microcapsule manufacture. These type of microcapsules appear to have the desired properties for investigating carcinogen exposure in the mammalian gastrointestinal tract. They can be prepared easily and reproducibly, contain sufficient magnetite to allow their facile recovery from aqueous suspensions, are easily broken to release soluble core polyethyleneimine, and are stable to hydrolytic enzymes (trypsin) in vitro.

Carcinogens↗
PubMed1986

Mutagenicity of the phenacetin metabolites: N-hydroxy-p-phenetidine and nitrosophenetol in S. typhimurium TA100 and derivatives deficient in nitroreductase or O-acetylase: probes for testing intrabacterial metabolic activation.

Two mutagenic metabolites of phenacetin, p-nitrosophenetol and N-hydroxy-p-phenetidine, were tested in S. typhimurium strains TA100, its nitroreductase-deficient derivative TA100NR, and O-acetylase-deficient strains TA100 Tn5-1,8-DNP1011 and -DNP1012 in the presence or absence of an exogenous metabolic activation system. The results indicate that bacterial nitroreductase(s) and O-acetylase(s), shown to be involved in the conversion of certain nitroarenes, are not required for the intrabacterial activation of the two phenacetin metabolites to bacterial mutagens. In view of the low reactivity of nitrosoarenes towards nucleophiles at neutrality, the mechanism by which they exert such a high mutagenic effect in S. typhimurium strains remains to be clarified, but is discussed.

Acetylesterase↗
PubMed1986

Identification, occurrence and mutagenicity in Salmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian chewing tobacco and betel quid.

During N-nitrosamine analysis of extracts of betel quid with tobacco and of the saliva of chewers of betel quid with tobacco for N-nitrosamines using a Thermal Energy Analyzer, two unknown compounds were detected. They were identified as synthetic nitro musks, musk ambrette (5-tert-butyl-1,3-dinitro-4-methoxy-2-methylbenzene, CAS No. 83-66-9) and musk xylene, (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, CAS No. 81-15-2), by gas chromatography-mass spectrometry and Fourier transform nuclear magnetic resonance spectroscopy. These compounds were detected in several samples of betel quid with tobacco and in perfumed tobacco used for chewing in India in amounts ranging from 0.45-23.5 mg/g wet weight. Musk ambrette was found to be mutagenic in Salmonella typhimurium TA100 requiring metabolic activation by rat-liver postmitochondrial supernatant but musk xylene lacked mutagenicity.

Animals↗
PubMed1986

Role of different cytochrome P-450 isozymes in the demethylation of various substrates.

Phenobarbital treatment of rats enhanced 2-fold the hepatic aninopyrine (AP) and dimethylhydrazine (DMH) demethylation but not that of N-nitrosodimethylamine (NDMA). Pyrazole enhanced the demethylation rate of DMH and NDMA but not that of AP. The in vitro effects of metyrapone and SKF-525A on the demethylation rate of various substrates were dependent on the substrate and treatment of rats. The data suggest that the demethylation of various substrates might be catalyzed by different cytochrome P-450 isozymes.

1,2-Dimethylhydrazine↗
PubMed1986

Quantitation and characterization of gamma-interferon receptors on human tumor cells.

The vast majority (71 of 77) of human tumor cells derived from various tissue origins were found to express specific membrane receptors for gamma-interferon (IFN-gamma). Six receptor-negative tumors were found among leukemic cells of lymphoid origin. Scatchard analysis with 125I-labeled human recombinant IFN-gamma revealed a similar binding affinity with a mean dissociation constant (Kd) of around 2 X 10(-11) M not only for various established cell lines, but also for leukemic and carcinoma cells derived from biopsy material. In contrast to similar KdS, large differences in the number of expressed IFN-gamma membrane receptors were found on distinct tumor cells of the same cell type ranging from a few hundred up to 2 X 10(4) for both carcinoma cells and leukemic cells. For comparison, the IFN-gamma receptor number on normal lymphocytes (mean, approximately 300/cell) and normal bone marrow cells (mean, approximately 1000/cell) was consistently found to be low. Cross-linking of membrane-bound 125I-IFN-gamma with disuccinimidyl suberate and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed, in both leukemia and carcinoma cells, three distinct complexes with molecular weights of approximately 70,000, 92,000, and 160,000, suggesting the existence of IFN-gamma receptor subunits. A dimeric structure of the functional IFN-gamma receptor with an estimated molecular weight of about 128,000 +/- 10,000 is proposed. Together with the Scatchard analysis, these data suggest the existence of a single class of high affinity IFN-gamma receptors in tumor cells of distinct tissue origin.

Cell Line↗
PubMed1986

Monoclonal antibody-directed analysis of cytochrome P-450-dependent monooxygenases and mutagen activation in the livers of DBA/2 and C57BL/6 mice.

Monoclonal antibodies (MAb 1-7-1 and Mab 2-66-3) specific for cytochrome P-450 (cyt. P-450) isozymes inhibited the metabolism of carcinogens, other xenobiotics, and endogenous compounds in two strains of mice. Postmitochondrial liver supernatant (S9) was prepared from untreated, 3-methylcholanthrene-treated, phenobarbital-treated, and pregnenolone 16 alpha-carbonitrile-treated C57BL/6 (B6) and DBA/2 (D2) mice. The modifying effect of two types of MAb to a 3-methylcholanthrene-induced cyt. P-450 and a phenobarbital-induced cyt. P-450 was investigated for: (a) S9-mediated mutagenicity of aflatoxin B1, benzo(a)pyrene 7,8-dihydrodiol, 2-acetylaminofluorene, and N-nitrosomorpholine in Salmonella typhimurium strains; and (b) the activity of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, aminopyrine N-demethylase, and testosterone 6 beta-, 7 alpha-, and 16 beta-hydroxylases. With certain S9s, MAb-1-7-1 inhibited only those cytochrome P-450 isozymes involved predominantly in activity of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase, and ethoxycoumarin O-deethylase and mutagenicity of 2-acetylaminofluorene and benzo(a)pyrene 7,8-dihydrodiol; MAb 2-66-3 inhibited only those involved in aminopyrine N-demethylase and testosterone 6 beta-, 7 alpha, and 16 beta-hydroxylase activity and aflatoxin B1 mutagenicity. Both Mab 1-7-1 and MAb 2-66-3 inhibited cytochrome P-450 isozyme(s) implicated predominantly in testosterone 7 alpha-hydroxylation in S9 from pregnenolone 16 alpha-carbonitrile-treated B6 mice. MAb 1-7-1 did not inhibit N-nitrosomorpholine mutagenicity and MAb 2-66-3 increased it by 2- to 6-fold depending on the source of S9. Using these MAbs, it is thus possible to identify the contribution of the epitope-defined single or class of cyt. P-450 to specific metabolic reactions in S9 from untreated and inducer-treated mice.

Animals↗
PubMed1986

Mutagenic and promutagenic properties of DNA adducts formed by vinyl chloride metabolites.

Published results and work from this laboratory permit the characterization of the possible promutagenic lesions induced by chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), both known as bifunctional alkylating metabolites of vinyl chloride (VC). The mutagenic effectiveness of CEO and CAA in Escherichia coli, when compared to their nucleophilic selectivity, suggests that the critical target site in DNA bases is not an oxygen atom, and/or that the reaction mechanism of CEO and CAA is different from a simple alkylation. CEO-mutagenicity in E. coli is recA-independent, and CEO preferentially induces GC----AT transitions; accordingly, the mutagenicity of CEO in bacteria may result mainly from a miscoding guanosine or cytosine adduct. Two observations argue against the role of 1,N6-ethenoadenine (epsilon A) and 3,N4-ethenocytosine (epsilon C) in VC-induced mutagenesis/carcinogenesis: i) the lack of detection in double-stranded DNA in vivo and in vitro; ii) the inconsistency between mutational specificity of CEO and miscoding properties of epsilon A and epsilon C. The lack of miscoding properties of 7-(2-oxoethyl)guanine (oxet-G), the major in-vivo VC-DNA adduct, suggests a minor miscoding base adduct. Several lines of evidence point to N4-(2-chlorovinyl)cytosine as one possible putative promutagenic lesion produced by VC, but this compound has yet to be identified in DNA.

Acetaldehyde↗