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  • 1
    Electronic Resource
    Electronic Resource
    Stimulation of cell division in the rat by NaCl, KCl, MgCl2, and CaCl2, and inhibition of the sodium chloride effect on the glandular stomach by ascorbic acid and β-carotene (1999)
    Springer
    Journal of cancer research and clinical oncology 125 (1999), S. 209-213 
    Details
    ISSN: 1432-1335
    Keywords: Key words Cell division ; Stomach ; Neoplasms ; Sodium chloride ; Ascorbic acid ; β-carotene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three questions associated with the stimulation of cell division by chloride salts have been investigated: (i) whether cations other than sodium show a similar effect, (ii) whether vitamins can have a preventive activity, and (iii) whether subchronic treatment with sodium chloride in the diet is also effective. Male Fischer 344 rats were given solutions of the chloride salts of sodium, potassium, magnesium, and calcium by oral gavage. Water was used for control. After 4 h, a 24-h osmotic minipump containing 5-bromo-2′-deoxyuridine was implanted subcutaneously. The forestomach and glandular stomach, as well as liver and bladder were analyzed immunohistochemically 24 h later for the proportion of cells in S phase as an indicator of the rate of replicative DNA synthesis. For both the forestomach and the glandular stomach, potassium was as potent as sodium, and the divalent cations Mg and Ca were even more potent on a molar basis. Supplementation of the diet with ascorbic acid (2 g/kg food) or β-carotene (12.5 mg/kg food) for 1 week before gavage of the sodium chloride solution resulted in an inhibition of the stimulation of cell division. A putative tumor-chemopreventive activity of the two vitamins might therefore not only rely on their antioxidative properties but may include effects on the cell cycle. A 4-week treatment with a sodium chloride supplement in the diet (2% and 4% supplement) resulted in a significant stimulation of cell division not only in both parts of the stomach and in the bladder (with the 4% supplement) but also in the liver (even with the 2% supplement). Sodium-chloride-stimulated cell turnover therefore is a sustained effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050264
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT1D subtype (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 371-377 
    Details
    ISSN: 1432-1912
    Keywords: Noradrenaline release ; Serotonin receptors ; 5-HT1D receptor ; Presynaptic receptors ; Human saphenous vein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The human saphenous vein preincubated with [3H]noradrenaline was used to determine the pharmacological properties of the release-inhibiting presynaptic serotonin (5-HT) receptor on the sympathetic nerves. The overflow of tritium evoked by transmural electrical stimulation (2 Hz) was concentration-dependently inhibited by drugs known to stimulate 5-HT receptors in the following rank order: oxymetazoline ≥ 5-HT ≥ 5-carboxamidotryptamine = 5-methoxytryptamine = sumatriptan 〉 tryptamine 〉 N,N(CH3)2-5-HT = yohimbine = 8-hydroxy-2-(di-n-propylamino)-tetraline. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B and 5-HT1D binding sites, but not with those for 5-HT1A or 5-HT1C binding sites. 5-Aminotryptamine, methysergide, ipsapirone, cyanopindolol, SDZ 21009 and metergoline dit not produce a significant inhibition. Metitepine and methysergide antagonized the inhibitory effect of 5-HT, whereas spiroxatrine, propranolol, ketanserin and ICS 205-930 did not. These data exclude the idea that the inhibitory presynaptic 5-HT receptor on the sympathetic nerves belongs to the 5-HT2 and 5-HT3 receptor class; the pattern of agonist potencies suggests that the receptor is very similar to the 5-HT1D receptor subtype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169451
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  • 3
    Electronic Resource
    Electronic Resource
    Tests for mutagenicity in salmonella and covalent binding to DNA and protein in the rat of the riot control agent o-chlorobenzylidene malononitrile (CS) (1981)
    Springer
    Archives of toxicology 49 (1981), S. 15-27 
    Details
    ISSN: 1432-0738
    Keywords: o-Chlorobenzylidene malononitrile ; Riot control agents ; DNA Binding ; Salmonella/microsome assay ; Carcinogens ; Mutagens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine whether o-chlorobenzylidene malononitrile (CS) exhibits any genotoxic activity towards Salmonella or mammalian DNA in vivo. CS was synthesized with a [14C]-label at the benzylic carbon atom. It was administered i.p. at a dose level of 13 mg/kg (1 mCi/kg) to young adult male rats. Liver and kidney DNA was isolated after 8,25, and 75 h. The radioactivity was at (liver, 8 and 75 h) or below (all other samples) the limit of detection of 3 dpm. Therefore, a possible binding of CS to DNA is at least 105 times lower than that of the strong hepatocarcinogen aflatoxin B1, and 4,000 times lower than that of vinyl chloride. In contrast to this lack of DNA binding, but in agreement with the chemical reactivity of CS, a binding to nuclear proteins could be detected with specific activities ranging between 50 and 121 dpm/mg for liver and between 3 and 41 dpm/mg for kidney. Protein binding could well be responsible for its pronounced cytotoxic effects. CS was also tested in the Ames Salmonella/microsome assay. Strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100 were used with or without pre-incubation. Only with strain TA 100 and only without pre-incubation, a doubling of the number of revertants was detectable at the highest dose levels used, 1,000 and 2,000 μg CS per plate. With pre-incubation of TA 100 with CS, a slight increase of the number of revertants was seen at 100 and 500 μg per plate, and a subsequent fall below control values at 1,000 μg. A check for the number of surviving bacteria revealed a strong bacteriotoxicity of the higher doses of CS so that the calculated mutation frequencies, i.e., the number of revertants per number of surviving bacteria, increased with doses up to 500 μg. This toxicity could be counteracted in part by the addition of increasing amounts of rat liver microsomes. In the view of these results, and taking into account the rare and low exposure of man, it is concluded that CS will not create a risk for the induction of point mutations or of carcinogenic processes mediated by DNA binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00352067
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  • 4
    Electronic Resource
    Electronic Resource
    Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro (1984)
    Springer
    Archives of toxicology 55 (1984), S. 97-103 
    Details
    ISSN: 1432-0738
    Keywords: Estrogen ; Hormone ; Carcinogenesis ; DNA binding ; Protein binding ; Estrone ; Estradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract [6,7-3H] Estrone (E) and [6,7-3H]estradiol-17β (E2) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E2 were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 μg/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (μmol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E2, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E2, respectively. The values for male hamster kidney were 〈 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate. Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 103–104 have been found for potent, 102 for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346046
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of inhalation exposure regimen on DNA binding potency of 1,2-dichloroethane in the rat (1991)
    Springer
    Archives of toxicology 65 (1991), S. 169-176 
    Details
    ISSN: 1432-0738
    Keywords: 1,2-Dichloroethane ; Carcinogens ; DNA binding ; Rat ; Inhalation ; Dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,2-Dichloroethane (DCE) was reported to be carcinogenic in rats in a long-term bioassay using gavage in corn oil (24 and 48 mg/kg/day), but not by inhalation (up to 150–250 ppm, 7 h/day, 5 days/week). The daily dose metabolized was similar in the two experiments. In order to address this discrepancy, the genotoxicity of DCE was investigated in vivo under different exposure conditions. Female F-344 rats (183–188 g) were exposed to [1,2-14C]- DCE in a closed inhalation chamber to either a low, constant concentration (0.3 mg/l=80 ppm for 4 h) or to a peak concentration (up to 18 mg/l=4400 ppm) for a few minutes. After 12 h in the chamber, the dose metabolized under the two conditions was 34 mg/kg and 140 mg/kg. DNA was isolated from liver and lung and was purified to constant specific radioactivity. DNA was enzymatically hydrolyzed to the 3′-nucleotides which were separated by reverse phase HPLC. Most radioactivity eluted without detectable or with little optical density, indicating that the major part of the DNA radioactivity was due to covalent binding of the test compound. The level of DNA adducts was expressed in the dose-normalized units of the Covalent Binding Index, CBI = (μmol adduct per mol DNA nucleotide/mmol DCE per kg body wt. In liver DNA, the different exposure regimens resulted in markedly different CBI values of 1.8 and 69, for “constant-low” and “peak” DCE exposure levels. In the lung, the respective values were 0.9 and 31. It is concluded that the DNA damage by DCE depends upon the concentration-time profile and that the carcinogenic potency determined in the gavage study should not be used for low-level inhalation exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02307305
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  • 6
    Electronic Resource
    Electronic Resource
    Simultane spirographische und blutgasanalytische Untersuchungen bei der Silikose unter Arbeitsbelastung (1957)
    Springer
    International archives of occupational and environmental health 16 (1957), S. 86-101 
    Details
    ISSN: 1432-1246
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Im Mittelpunkt der klinischen Beurteilung und Begutachtung der Staublungenerkrankungen und ihrer Folgeerscheinungen stehen einmal eine sorgfältige Röntgenuntersuchung und zum anderen die eingehende Funktionsdiagnostik. Als Leistungsprüfung hat sich neben anderen Verfahren die Ergospirographie allgemein eingebürgert und bewährt. Besonderes Interesse hat in diesem Zusammenhang die Frage gefunden, ob eine Relation zwischen einem spirographischen Sauerstoffdefizit und einer arteriellen O2-Untersättigung besteht. Auf Grund simultaner spirographischer und blutgasanalytischer Untersuchungen unter Arbeitsbelastung bei 17 Probanden, zum überwiegenden Teil mit einer mittelgradigen Silikose, ergab sich, daß ein spirographisches Sauerstoffdefizit eine arterielle O2-Untersättigung zur Voraussetzung hat. Einzelfälle werden mit Originalkurven belegt und die Vorzüge beider Verfahren diskutiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318021
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  • 7
    Electronic Resource
    Electronic Resource
    Endogenous and exogenous factors in carcinogenesis: limits to cancer prevention (1996)
    Springer
    International archives of occupational and environmental health 68 (1996), S. 120-125 
    Details
    ISSN: 1432-1246
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Organ-specific cancer incidence rates can vary dramatically between low- and high-incidence areas. Such differences are due to (1) heritable susceptibility determinants, (2) risk factors associated with the environmental and local living conditions (e.g., viruses, pollution), and (3) personal life-style factors. For organs showing large differences between cancer registries, exogenous factors might be most important, while for organs showing only small differences, endogenous and unavoidable factors are expected to be more important. In this paper, a working hypothesis based on descriptive cancer epidemiology is presented to estimate, in a quantitative manner, the unavoidable contribution to the process of carcinogenesis and to discuss limitations to individual cancer prevention. Cumulative cancer incidence rates for a 75-year period of life (CR74, in percent) were taken from IARC Scientific Publication No. 120 (1992). For each organ, values were ranked in ascending order, and the ratio between high-rate and low-rate registries (90th percentile/10th percentile) was determined. This measure of variability among registries differed strongly between organs. Largest ratios were seen for organs with well-known exogenous risk factors, such as pharynx, lip, tongue, mouth, liver, esophagus, and melanoma in males, and lung, esophagus, gallbladder, liver, and bladder in females. Small ratios were seen for rectum, brain, colon, and Hodgkin's disease in males, and breast, rectum, ovary, brain, and colon in females. It is concluded that the process of carcinogenesis in the latter organs has a stronger endogenous/unavoidable component, for some tissues possibly of hormonal type. A fictitious population was composed where, for each organ, the minimum reported cancer rate was taken. When based on all cancer registries world-wide, CR74 sums over all sites of 2.0% and 2.3% resulted in males and females, respectively. When only Central/Western European countries were included in the analysis in order to reduce differences in risk factors nos, 1 and 2, the sum of the minimum values was 10.4% and 8.7%. After correction of the data for smoking, ‘minimum’ cancer incidence rates in males and females were estimated to be 7.6% and 6.8%. Based on a median cancer incidence rate for nonsmoking males in Europe of about 21%, therefore, individual preventive measures taken by a nonsmoker can reduce the cancer risk, on average, ‘only’ by a factor of about 3. A considerable fraction of cases thus appears to be hardly avoidable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381244
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  • 8
    Electronic Resource
    Electronic Resource
    Kritische Bemerkungen zur Diagnostik des Lungenemphysems bei Kohlenbergarbeitern (1959)
    Springer
    International archives of occupational and environmental health 17 (1959), S. 442-456 
    Details
    ISSN: 1432-1246
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00388010
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  • 9
    Electronic Resource
    Electronic Resource
    Lungenvolumina und Lungenzeitvolumina bei Kohlenbergarbeitern (1959)
    Springer
    International archives of occupational and environmental health 17 (1959), S. 396-419 
    Details
    ISSN: 1432-1246
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00388007
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  • 10
    Electronic Resource
    Electronic Resource
    Technical and biological recultivation and development of exhausted open cast mines in the German Democratic Republic (1984)
    Springer
    GeoJournal 8 (1984), S. 75-79 
    Details
    ISSN: 1572-9893
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography
    Notes: Abstract The production of lignite required for the GDR's national economy calls for the shifting of more than a thousand million cubic metres of overburden and the raising of about 1.5 thousand million m3 of ground-water. The ecological and infrastructural consequences are drastic, particularly in the Bezirke of Cottbus, Leipzig and Halle, where most lignite mines are situated. Planned reclamation of exhausted mining areas has so far permitted more than 50,000 ha in the GDR to be returned to agricultural and forestry use. Several attractive recreational areas have been developed by making use of exhausted workings that have been flooded. An outline is given of the legislation governing the responsibilities of the mining enterprises for the reclamation of devastated regions. The work to be done by the agricultural, forestry and water management enterprises to which the reclaimed areas are handed over for final recultivation is described, and the landscape management by which such former open cast mines can be converted into valuable amenities and economically viable regions are discussed in some detail.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00155613
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