Wynik wyszukiwania w bazie Polska Bibliografia Lekarska GBL

Zapytanie: PIOSIK
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Tytuł oryginału: The modulation of the DNA-damaging effect of polycyclic aromatic agents by xanthines. P. 1: Reduction of cytostatic effects of quinacrine mustard by caffeine.
Autorzy: Kapuściński Jan, Ardelt Barbara, Piosik Jacek, Zdunek Małgorzata, Darzynkiewicz Zbigniew
Źródło: Biochem. Pharmacol. 2002: 63 (4) s.625-634, il., tab., bibliogr. 45 poz.
Sygnatura GBL: 304,395

Hasła klasyfikacyjne GBL:
  • genetyka
  • farmacja

    Typ dokumentu:
  • praca kliniczna
  • praca opublikowana za granicą
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • ludzie

    Streszczenie angielskie: Recently, accumulated statistical data indicate the protective effect of caffeine consumption against several types of cancer diseases. There are also reports about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. However, there is also numerous data indicating reverse effect on cytotoxicity of anticancer drugs that inhibit the action of topoisomerase I (e.g. Camptothecin or Topotecan) and topoisomerase II inhibitors (e.g. Doxorubicin, Mitoxantrone or mAMSA). In this work we tested the hypothesis that the caffeine protective effect is the result of sequestering of aromatic mutagens by formation of stacking (ă - ă) complex. As the models for the study we have chosen two well-known mutagens, that do not require metabolic activation: quinacrine mustard (QM, aromatic, heterocyclic nitrogen mustard) and mechlorethamine (NM2, aliphatic nitrogen mustard). The flow cytometry study of these agents' action on the cell cycle of HL-60 cells indicated that caffeine prevents the cytotoxic action of QM, but not that of NM2. The formations of stacking complexes of QM with caffeine were confirmed by light absorption, calorimetric measurements and by molecular modeling calculation. Using the statistical thermodynamics calculations we calculated the "neighborhood" association constant (KAC = 59 ń 2 M**-1) and enthalpy change (DeltaH**0' = -116 cal mol**-1); the favorable entropy change of complex formation (DeltaS**0' = 7.72 cal mol**-1 K**-1, ...

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    Tytuł oryginału: The modulation by xanthines of the DNA-damaging effect of polycyclic aromatic agents. P. 2: The stacking complexes of caffeine with doxorubicin and mitoxantrone.
    Autorzy: Piosik Jacek, Zdunek Małgorzata, Kapuściński Jan
    Źródło: Biochem. Pharmacol. 2002: 63 (4) s.635-646, il., tab., bibliogr. 45 poz.
    Sygnatura GBL: 304,395

    Hasła klasyfikacyjne GBL:
  • farmacja

    Typ dokumentu:
  • praca doświadczalna
  • praca opublikowana za granicą
  • tytuł obcojęzyczny

    Streszczenie angielskie: Recently accumulated statistical data indicate the protective effects of caffeine consumption against several types of cancer diseases. There are also reports, about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations of this phenomenon is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. In the accompanying paper [Kapuścinski et al., this issue] we provide evidence (flow cytometry and the cell cycle analysis) that the cytostatic effects of caffeine (CAF) on two DNA alkylating agents, which do not require the biological activation, depend on their ability to form stacking (ă - ă) complex. In this study, we use physicochemical techniques (computer aided light absorption and microcalorimetry), and molecular modeling to examine previously published qualitative data. This is published both by our and other group's data, indicates that CAF is able to modify the cytotoxic and/or cytostatic action of the two well known antitumor drugs doxorubicin (DOX) and mitoxantrone (MIT). To obtain the quantitative results from the experimental data we used the statistical-thermodynamical model of mixed aggregation, to find the association constants KAC of the CAF-drug interaction (128 ń 10 and 356 ń 21 M**-1 for DOX-CAF and MIT-CAF complex formation, respectively). In addition, the favorable enthalpy change of CAF-MIT (DeltaH = -11.3 kcal/mol) was measured by microcalorimetry titration. The molecular modeling (semi-empirical and force field method)...

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