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H Bartsch

Publications and source records attributed to H Bartsch.

At least 343 records · Page 19Linked to original sources
PubMed1986

Detection of DNA base damage by 32P-postlabelling: TLC separation of 5'-deoxynucleoside monophosphates.

Traces of damaged bases in DNA can be detected without the use of radioactive chemical agent or radiolabelled DNA substrate by incorporation of radiolabel into DNA after exposure to the chemical. This postlabelling approach to carcinogen adduct analysis is potentially useful for adduct detection in the DNA of humans exposed to carcinogens. We describe here the postlabelling analysis of DNA by chromatography of deoxynucleoside monophosphates. Separation and characterization of modified residues in nucleotide digests of DNA treated in vitro with chloroacetaldehyde is demonstrated.

Acetaldehyde↗
PubMed1986

Reaction kinetics and cytosine adducts of chloroethylene oxide and chloroacetaldehyde: direct observation of intermediates by FTNMR and GC-MS.

As it is not yet known which are the important miscoding adducts formed in the reaction of the relatively unstable compound chloroethylene oxide (CEO) with double-stranded DNA, proton FTNMR and GC-mass spectroscopy were used to directly detect and characterize reaction intermediates. Reaction of CEO with cytidine gave the (hydrated) 2-oxoethyl derivative at the N-3 position prior to ring closure to 3,N4-ethenocytidine; 5-methylcytosine gave an analogous reaction. However, reactions of CEO or chloroacetaldehyde (CAA) with 3-methylcytidine - i.e., with the N-3 blocked as in double-stranded DNA (ds DNA) - were shown by GC-MS of the silylated products to give, at a much slower rate, a pattern of at least 17 adducts all of which contained chlorine. Based on MS fragmentation and considerations of positional, optical and cis/trans isomerism, the reaction products of the 3-methylcytosine moiety were assigned as cis/trans N4-(2-chlorovinyl)-3-methylcytosine which may have arisen from the corresponding N4-(1-hydroxy-2-chloroethyl) adduct. It is postulated that formation of these cytosine-N4 adducts would be more rapid in double-stranded DNA than in the model compound, and that the N4-(2-chlorovinyl) group may be a miscoding adduct. The kinetics for CEO rearrangement, hydrolysis and nucleophilic attack have been studied by proton FTNMR and lead to the hypothesis that concerted nucleophilic attack by cytosine-N4 and CEO rearrangement produce the N4 adducts.

5-Methylcytosine↗
PubMed1986

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C.

A total of 238 samples of 24-h urine were collected from inhabitants of high-risk (Lin-xian) and low-risk (Fan-xian) areas for esophageal cancer in northern China, according to three protocols: (a) from undosed subjects; (b) from subjects who had ingested 100 mg L-proline three times a day 1 h after each meal; and (c) from subjects in Lin-xian who had ingested 100 mg ascorbic acid together with 100 mg L-proline three times a day 1 h after each meal. As an index of individual exposure to N-nitroso compounds or their precursors, ingested in food and/or formed endogenously, the levels of four urinary N-nitrosamino acids and nitrate were determined. The amounts of N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, N-nitrososarcosine, and nitrate excreted in the 24-h urine of undosed subjects in Lin-xian were significantly higher than those in Fan-xian, indicating a higher exposure of the inhabitants in the high-risk area to N-nitroso compounds and their precursors. Ingestion of L-proline resulted in a marked increase in urinary N-nitrosoproline levels in inhabitants from both areas, suggesting that endogenous nitrosation may occur to a larger extent when appropriate amine precursors are ingested in foods. Intake of moderate doses of ascorbic acid by high-risk subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area. If N-nitroso compounds formed in vivo are among the causative factors for esophageal cancer in this area of northern China, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds, thus offering a rational basis for long-term intervention studies in this area.

Adult↗
PubMed1985

Biological effects of gamma-interferon on human tumor cells: quantity and affinity of cell membrane receptors for gamma-IFN in relation to growth inhibition and induction of HLA-DR expression.

A large difference in the number of gamma-IFN receptors was found on a variety of human tumor cell lines with a range of 0.4 to 15 X 10(3) binding sites/cell. The receptor number did not correlate with the potential responsiveness of the cells to gamma-IFN, in regard to either growth inhibition or induction of HLA-DR expression, two independently regulated gamma-IFN effects. However, with respect to HLA-DR expression it was found that the gamma-IFN sensitivity of inducible cell lines depended on the number of receptors, so that with increasing number of receptors present on these cells lower doses of gamma-IFN were required for induction of the gamma-IFN effect.

Cell Division↗
PubMed1985

Oesophageal cancer studies in the Caspian littoral of Iran: some residual results, including opium use as a risk factor.

A study was conducted in northern Iran in areas of very high, high and moderately low incidence of oesophageal cancer. Morphine metabolites in urine as an indicator of opium use, and a variety of nutritional and biochemical measures, including salivary antipyrine half-life, were determined in households with a case of oesophageal cancer and in control households. Results on 1,590 individuals showed that the prevalence of appreciable levels (greater than or equal to 1 microgram/ml) of urinary morphine metabolites was much higher in areas of high and very high incidence of oesophageal cancer than in low-incidence areas, particularly for those under age 50 years in both sexes, where a 6-fold difference was seen. Members of households with a case of oesophageal cancer had a higher prevalence of positive urinary morphine metabolite findings than members of control households from the same village. Salivary anti-pyrine half-life (AP-T1/2), as a measure of hepatic drug metabolizing capacity, was estimated in 120 subjects. No relationship was seen with use of opium, region of residence, case-control status of household, age or sex. Experimental studies have meanwhile identified mutagenic substances with carcinogenic potential in opium pipe scrapings, used widely in the study region, opium pyrolysates and morphine pyrolysates. Our data give additional support to the hypothesis that opium use, in the form of its pyrolysates, is one of the factors involved in the aetiology of oesophageal cancer in the region.

Adolescent↗
PubMed1985

Identification and occurrence of two new N-nitrosamino acids in tobacco products: 3-(N-nitroso-N-methylamino)propionic acid and 4-(N-nitroso-N-methylamino)butyric acid.

Two new N-nitrosamino acids, 3-(N-nitroso-N-methylamino)propionic acid (CAS: 10478-42-9) and 4-(N-nitroso-N-methylamino)butyric acid (CAS: 61445-55-4) were isolated and identified for the first time in various types of tobacco, including snuff, chewing and pipe tobacco, cigars and cigarettes. Their levels ranged from 0.15 to 7.4 and 0 to 2.2 mg/kg of dry weight tobacco, respectively. For comparison, amounts of other N-nitrosamino acids like N-nitrosoproline (NPRO) and tobacco-specific-nitrosamines (TSNA) were determined in the same samples. The levels of N-nitrosamino acids were highly correlated with the levels of TSNA.

Chromatography, Gas↗
PubMed1985

Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid.

In order to evaluate exposure of betel quid chewers to N-nitroso compounds, saliva and urine samples were collected from chewers of betel quid with or without tobacco, from tobacco chewers, from cigarette smokers and from people with no such habit, and were analysed for the presence of N-nitrosamines by gas chromatography coupled with Thermal Energy Analyzer and alkaloids derived from betel nut and tobacco by capillary gas chromatography fitted with nitrogen-phosphorous selective detector. The levels of the betel nut-specific nitrosamines, N-nitrosoguvacoline and N-nitrososoguvacine (the latter being detected for the first time in saliva), ranged from 0 to 7.1 and 0 to 30.4 ng/ml, respectively. High levels of tobacco-specific nitrosamines were detected in the saliva of chewers of betel quid with tobacco and in that of chewers of tobacco, ranging from 1.6 to 59.7 (N'-nitrosonornicotine), 1.0 to 51.7 (N'-nitrosoanatabine) and 0 to 2.3 [4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone] ng/ml. Urinary concentrations of certain N-nitrosamino acids, including N-nitrosoproline, were determined as a possible index of exposure to nitroso compounds and their precursors in the study groups: no clear difference was observed. The betel nut-specific alkaloid, arecoline, was present at high levels in the saliva of betel quid chewers with or without tobacco. Nicotine and cotinine were also detected in saliva and urine of chewers of tobacco and of betel quid with tobacco. In order to assess whether N-nitroso compounds are formed in vivo in the oral cavity during chewing or in the stomach after swallowing the quids, the levels of N-nitroso compounds in betel quid extracts were determined before and after nitrosation at pH 7.4 and 2.1. The results indicate that N-nitroso compounds could easily be formed in vivo. The possible role of N-nitroso compounds in the causation of cancer of the upper alimentary tract in betel quid chewers is discussed.

Adult↗
PubMed1985

Screening of microorganisms for nitrosation catalysis at pH 7 and kinetic studies on nitrosamine formation from secondary amines by E. coli strains.

Thirty-eight strains of microorganisms isolated from infected human trachea, urine, blood and faeces were examined for their ability to form N-nitrosomorpholine from morpholine and nitrite at pH 7.25. Twenty-five bacterial strains exhibited nitrosation activity, including 18 out of 19 strains of Escherichia coli and three out of nine Pseudomonas aeruginosa, Proteus morganii, Proteus mirabilis, Klebsiella pneumoniae and Neisseria strains; E. coli A10 strain showed the highest activity. Formation of N-nitrosomorpholine was proportional to the incubation time up to 2 h and to the number of resting E. coli A10 cells; the reaction followed Michaelis-Menten kinetics. Nitrosation rate appeared to be dependent on the pKa value of several amines studied. As the nitrosation catalysis was heat-labile, our data suggest that N-nitrosation is catalysed by a bacterial enzyme(s). This reaction may lead to enhanced endogenous nitrosation in subjects suffering from an achlorhydric stomach or from chronic urinary tract infections.

Amines↗
PubMed1985

Evidence for modulation of melatonin secretion in men with benign and malignant tumors of the prostate: relationship with the pituitary hormones.

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean-cosinor method, and linear correlation coefficients between the five hormones were calculated for each group. Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty-four-hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.

Aged↗
PubMed1985

Differential gamma-interferon response of human colon carcinoma cells: inhibition of proliferation and modulation of immunogenicity as independent effects of gamma-interferon on tumor cell growth.

The effect of recombinant gamma-interferon (IFN-gamma) on established human colon carcinoma cell lines as well as fresh tumor cells from colon carcinoma patients has been investigated with respect to growth inhibition, enhancement of HLA expression, and modulation of immunogenicity. A direct antiproliferative activity of IFN-gamma was observed in five of seven cell lines tested, with a reduction of [3H]thymidine incorporation between 30 and 90%. Depending on the cell line, the IFN-gamma doses required for maximal inhibition varied between 20 and 2 X 10(4) units/ml. Independent of this effect, IFN-gamma enhanced the expression of HLA-A,B,C antigens in all cells investigated and induced expression of HLA-DR in three of seven carcinoma cell lines. Antigenic modulation of Class I and II major histocompatibility complex antigens was paralleled by an enhancement of the in vitro immunogenicity in three of four established carcinoma lines and in three of three cases, using cells derived from primary tumor cultures. Induction or enhancement of both proliferative and cytolytic T-cell responses was obtained in allogeneic and in autologous mixed-lymphocyte tumor cell cultures.

Adenocarcinoma↗
PubMed1985

Lack of miscoding properties of 7-(2-oxoethyl)guanine, the major vinyl chloride-DNA adduct.

Chloroethylene oxide, an ultimate carcinogenic metabolite of vinyl chloride, was reacted with poly(deoxyguanylate-deoxycytidylate); the nucleic acid base adducts, 7-(2-oxoethyl)guanine and 3,N4-ethenocytosine, were analyzed by reverse-phase high-performance liquid chromatography. Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I, and the newly synthesized product was subjected to nearest-neighbor analysis. Misincorporation rates of deoxyadenosine monophosphate and thymidine monophosphate were found to increase with the level of template modification. About 80% of the mispairing events were located opposite minor cytosine lesions. 7-(2-Oxoethyl)guanine, the major adduct identified (greater than 98% of the adducts), did not miscode for either thymine or adenine, failing to support an earlier hypothesis that the cyclic hemiacetal form, O6,7-(1'-hydroxyethano)guanine, could, by analogy with O6-methyl- and O6-ethylguanine, simulate adenine. Our results indicate that direct miscoding of 7-(2-oxoethyl)-guanine may contribute only slightly to the induction of mutations by chloroethylene oxide or vinyl chloride.

Chromatography, High Pressure Liquid↗
PubMed1984

Occurrence in human urine of new sulphur-containing N-nitrosamino acids N-nitrosothiazolidine 4-carboxylic acid and its 2-methyl derivative, and their formation.

To quantitate endogenous nitrosation reactions in man, the quantity of N-nitrosoproline (NPRO) excreted in the urine after ingestion of proline and/or nitrate was estimated. When this monitoring method (NPRO test) was applied in clinical and field studies, several hitherto unidentified N-nitroso compounds were frequently detected. These were recently identified as sulphur-containing N-nitrosamino acids, N-nitrosothiazolidine 4-carboxylic acid (NTCA), and trans- and cis-isomers of N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA). NTCA and NMTCA were readily formed in vitro following nitrosation at acidic pH of the respective precursor, thiazolidine 4-carboxylic acid (TCA) or of 2-methylthiazolidine 4-carboxylic acid (MTCA). As the latter compounds can be formed by reaction of L-cysteine with formaldehyde or acetaldehyde, respectively, NTCA and NMTCA were also formed by reacting L-cysteine with the respective aldehyde and with nitrite at optimal pH (2.5 for NTCA and 4.5 for NMTCA). Up to 95% of NTCA and NMTCA given orally to fasted rats was recovered as such in urine and faeces within 2 days. Administration of TCA or MTCA, together with nitrite increased the urinary excretion of NTCA and NMTCA, as did co-administration of L-cysteine, nitrite, and the respective aldehyde. NTCA and NMTCA were also detected in the 24-h urine of human volunteers, and smokers tended to excrete higher levels than nonsmokers. Daily excretion levels varied, however, and a diet supplemented with ascorbic acid significantly decreased the total amount of nitrosamino acids. NTCA and NMTCA may occur in human urine as a result of (i) intake of preformed N-nitroso compounds; (ii) intake of thiazolidine 4-carboxylic acid or its 2-methyl derivative and subsequent nitrosation in vivo; (iii) endogenous two-step synthesis by the reaction of L-cysteine with the respective aldehyde and a nitrosating agent. Thus, measurement of NTCA and NMTCA together with NPRO in urine may provide an index for the exposure of human subjects to nitrosamines or their precursors, i.e., nitrosating agents, certain aldehydes, or aldehyde-generating compounds. Our data demonstrate unequivocally that N-nitroso compounds are formed in the human body, as suggested previously by Druckrey. Their relevance to human cancer at specific sites should now be investigated.

Administration, Oral↗
PubMed1984

Lack of mutagenicity of synthetic pyrethroids in Salmonella typhimurium strains and in V79 Chinese hamster cells.

Seven pyrethroids, i.e., cypermethrin, permethrin, deltamethrin, bioresmethrin, resmethrin, cismethrin and fenvalerate, were not found to be mutagenic in (a) Salmonella typhimurium strains TA100 or TA98 in the presence or absence of a rat liver activation system using the plate incorporation assay and fluctuation tests, or (b) V79 Chinese hamster cells in the presence or absence of hepatocytes.

Animals↗
PubMed1984

Metabolism and urinary excretion of mutagenic metabolites of benzo[a]pyrene in C57 and DBA mice strains.

Groups of C57Bl/6 (B6) mice (responsive) and DBA/2 (D2) (non-responsive) mice received an i.p. dose of benzo[a]pyrene (BP) (100 mg/kg body weight) with or without pretreatment with beta-naphthoflavone (BNF), an inducer of monooxygenases. The amount of mutagenic BP metabolites in the urine was determined by the Salmonella/microsome assay (strain TA100) and excretion of BP metabolites was quantified by h.p.l.c. After inducer treatment, the responsive mice excreted more mutagens and total oxidized BP metabolites in the urine than did the non-responsive strain. The ratio of BP diols:total oxidized metabolites was 0.42 in B6 mice and 0.72 in D2 mice and was not affected by inducer treatment. After a dose of [14C]BP, radioactivity was measured in the faeces for up to 7 days. The half-life of [14C]BP in the non-responsive D2 mice was about twice that in the responsive B6 mice. Our results agreed with a previously proposed model of the risk factors for toxic effects and/or the development of tumours after exposure to polycyclic aromatic hydrocarbons in responsive and non-responsive mouse strains.

Animals↗
PubMed1984

Possible involvement of a vicinal, non-bay-region dihydrodiol-epoxide in the activation of dibenzo[a,e]fluoranthene into bacterial mutagens.

Dibenzo[a,e]fluoranthene, its 7-hydroxy, 3,4- and 12,13-dihydrodiol metabolic derivatives as well as three synthetic, structurally related hydrocarbons, were tested for mutagenicity towards Salmonella typhimurium TA100 strain in the presence of 3-methylcholanthrene-treated rat and mouse liver post-mitochondrial supernatants. Of these compounds, the 12,13-dihydrodiol showed the highest activity, being 6-10 times more mutagenic than the parent compound. Our data, in conjunction with those of previous studies on the liver microsomal metabolism and DNA binding of dibenzo[a,e]fluoranthene and its dihydrodiols, indicate that activation of dibenzo[a,e]fluoranthene to bacterial mutagens may occur predominantly through a vicinal, non-bay-region 12,13-dihydrodiol epoxide.

Animals↗
PubMed1984

Dietary phenolics and betel nut extracts as modifiers of N-nitrosation in rat and man.

Polyphenolic compounds (PPC) isolated from betel nuts and some dietary PPC were examined for their modifying effects on N-nitrosation in vitro and in vivo. The formation of N-nitrosodiethylamine (NDEA) and N-nitrosoproline (NPRO) was either enhanced or inhibited by PPC from betel nuts, depending on (1) the structure of the PPC, (2) the pH of the reaction medium, (3) the relative concentrations of nitrite and PPC, and (4) the nature of the nitrosatable amino compounds. Both catalysis and inhibition of endogenous nitrosation of proline were observed in rats, although to a lesser extent than in vitro. Caffeic and ferulic acids, as well as the PPC-containing beverages tea and coffee, exerted inhibitory effects on endogenous formation of NPRO in two human subjects. These results demonstrate that PPC can modify the yield of endogenously formed N-nitroso compounds, and may thus effect the carcinogen burden in man.

Animals↗