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Zapytanie: ARDELT
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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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