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  • 1
    Electronic Resource
    Electronic Resource
    The change in carcinogenic effectiveness of some cyclic nitrosamines at different doses (1978)
    Springer
    Journal of cancer research and clinical oncology 92 (1978), S. 221-225 
    Details
    ISSN: 1432-1335
    Keywords: Rats ; Nitrosamines ; Carcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The carcinogenic effectiveness in rats of three cyclic nitrosamines administered at two doses separated by a factor of five has been studied. All three compounds showed a response at the lower dose quite different from that at the higher dose. One, 2,6-dimethyl-dinitrosopiperazine, was only a little less effective at the lower dose than at the higher dose, giving 100% nasal turbinate tumors, but only 33% esophageal tumors, compared with 100% esophageal tumors at the higher dose. 3,4-Dichloronitrosopiperidine gave 100% incidence of esophageal tumors at the higher dose. At the lower dose, survival of the rats was very much better, some living 80 weeks, and, in addition to the esophagus, there were tumors of several organs including forestomach, tongue, and nasal turbinates. On the other hand, 2,6-dimethylnitrosomorpholine was a very much weaker carcinogen at the lower than at the higher dose, only six animals dying with tumors, compared with 100% incidence at the higher dose. However, the pattern of mortality of rats given the lower dose of dimethylnitrosomorpholine was similar to that of rats given the lower dose of dichloronitrosopiperidine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00461644
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Distribution of the liver carcinogen methapyrilene in fischer rats and its interaction with macromolecules (1982)
    Springer
    Journal of cancer research and clinical oncology 103 (1982), S. 69-73 
    Details
    ISSN: 1432-1335
    Keywords: Methapyrilene ; Liver tumor ; Rat ; Interaction ; Radioactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anti-histaminic drug methapyrilene hydrochloride, which induces liver tumors in rats, was labeled with tritium by exchange and administered at a dose of 21 mg containing 700 μCi to each of 15 male Fischer rats. At 1 h, 6 h, 14 h, 24 h, and 44 h after treatment three rats were killed and their livers, pancreas, kidneys, and lungs were removed. The pooled organs were homogenized and DNA, RNA, and soluble protein were isolated from each. The extent of interaction of radioactive methapyrilene with liver nucleic acids was exceedingly small and did not differ significantly from the binding to nucleic acids in kidney, lung, or pancreas, which are not target organs of this carcinogen in rats. Binding of radioactivity to soluble proteins of the liver was considerable and substantially greater than in the other organs. If the mechanism of carcinogenic action of methapyrilene involves covalent interaction with DNA this must be at a very low and highly specific level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410307
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Deuterium isotope effects in carcinogenesis by N-nitroso compounds (1986)
    Springer
    Journal of cancer research and clinical oncology 112 (1986), S. 229-239 
    Details
    ISSN: 1432-1335
    Keywords: Deuterium ; Carcinogenesis ; N-nitroso compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A number of N-nitroso compounds and an azoxyalkane have been labeled with deuterium in various positions and have been administered to rats, hamsters, or mice in parallel with the unlabeled compounds. The treatments with the labeled and analogous unlabeled compounds were equimolar and for the same time. Mortality rates from tumors and tumor incidences were compared between deuteriumlabeled and the unlabeled analogs. In many cases more than one dose level was used for the comparisons. An increased rate of mortality from tumors or an increased incidence of induced tumors was considered an index of increased potency of one treatment compared with the other. Using these criteria deuterium in the alpha positions of nitrosodimethylamine, nitrosomorpholine, nitrosoheptamethyleneimine, and nitrosoazetidine reduced carcinogenic potency compared with the unlabeled compounds. This indicated that cleavage of a carbon-hydrogen bond in the alpha position was a rate-limiting step in carcinogenesis by these nitrosamines. In both nitrosomethylethylamine and nitroso-2,6-dimethylmorpholine, the presence of deuterium at different positions increased or decreased carcinogenic potency, suggesting that competition for oxidation between these sites might be the determining factor in activation of the molecule. This also applied to nitrosomethyl-n-butylamine and nitrosomethylphenylethylamine with deuterium at the methyl group or at the alpha carbon of the butyl or phenylethyl groups, and to azoxymethane with deuterium in the 1-methyl or 4-methyl group. In nitrosomethylcyclohexylamine, nitrosomethyl-n-dodecylamine, and dinitroso-2,6-dimethylpiperazine there was no detectable effect of deuterium on carcinogenic potency, suggesting that the conditions did not provide sufficient sensitivity for detection of an isotope effect, or that oxidation at the alpha carbon was not a rate-limiting step in carcinogenesis by these molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00395917
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  • 4
    Electronic Resource
    Electronic Resource
    Carcinogenesis in F-344 rats by nitrosobis(2-oxopropyl)amine and related compounds administered in drinking water (1984)
    Springer
    Journal of cancer research and clinical oncology 107 (1984), S. 178-182 
    Details
    ISSN: 1432-1335
    Keywords: Carcinogenesis ; F-344 Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three asymmetric nitrosamines related to nitrosobis-(2-oxopropyl)-amine (BOP) were given to female F 344 rats in drinking water to assess the significance of other alkyl groups on the carcinogenic expression by the 2-oxopropyl group. Nitroso-oxopropylethanolamine (OPE) was weakly carcinogenic, leading to little life-shortening and to induction of tumors (most of them liver neoplasms) in less than half of the treated animals. BOP under these conditions induced a high incidence of hepatocellular carcinomas and hemangiosarcomas of the liver together with lung adenomas in most animals. At the same dose rate nitrosohydroxypropyl-oxopropylamine (HPOP) induced hepatocellular carcinomas, lung carcinomas, and carcinomas of the esophagus with a high incidence; life-shortening was greater with HPOP than with BOP. At a higher dose rate HPOP again induced a high incidence of esophageal carcinomas, and of liver neoplasms, but more animals had hemangiosarcomas than hepatocellular carcinomas. Nitrosodihydroxypropyl-oxopropylamine (DHPOP) increased the mortality rate due to tumors by much more than the other three compounds, but induced mainly tumors of the upper gastrointestinal tract and no neoplasms in the liver. These results do not support the concept that BOP acts through reduction to HPOP, but suggest rather that the nature of the substituents other than 2-oxopropyl in the analogs of BOP has a profound influence on the potency and organ-specificity of the carcinogen. It is probable that pharmacokinetics and the specificity of activation of the particular molecular structures play an important role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01032604
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    Paper (German National Licenses)
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