Piosik Jacek, Ulanowska Katarzyna, Gwizdek-Wiśniewska Anna, Czyz Agata, Kapuściński Jan, Wegrzyn Grzegorz
Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kladki 24, 80-822 Gdańsk, Poland.
Mutat Res. 2003 Sep 29;530(1-2):47-57. doi: 10.1016/s0027-5107(03)00136-2.
Previous studies performed by others indicated that apart from its other biological effects, caffeine (CAF) may have a role in protection of organisms against cancer. However, biological mechanism of this phenomenon remained unknown. Recent studies suggested that caffeine can form stacking (pi-pi) complexes with polycyclic aromatic chemicals. Therefore, one might speculate that effective concentrations of polycyclic aromatic mutagens could be reduced in the presence of caffeine. Here we demonstrate that caffeine and another xanthine, pentoxifylline (PTX), effectively alleviate mutagenic action of polycyclic aromatic agents (exemplified by quinacrine mustard (QM), 2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine.2HCl (ICR-191) and 1,3,7-propanediamine-N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-9-acridinyl)-N-ethyl.2HCl (ICR-170)), but not of aliphatic mutagens (exemplified by mechlorethamine), in the recently developed mutagenicity test based on bacterium Vibrio harveyi. Biophysical studies indicated that caffeine and pentoxifylline can form stacking complexes with the aromatic agents mentioned above. Molecular modeling also confirmed a possibility of stacking interactions between examined molecules.
其他人之前进行的研究表明，咖啡因（CAF）除了具有其他生物学效应外，可能在保护生物体免受癌症侵害方面发挥作用。然而，这一现象的生物学机制仍然未知。最近的研究表明，咖啡因可以与多环芳烃化学物质形成堆积（π-π）复合物。因此，有人可能推测在咖啡因存在的情况下，多环芳烃诱变剂的有效浓度可能会降低。在此我们证明，在最近基于哈维氏弧菌开发的致突变性试验中，咖啡因和另一种黄嘌呤——己酮可可碱（PTX），能有效减轻多环芳烃试剂（以喹吖因氮芥（QM）、2-甲氧基-6-氯-9-（3-（2-氯乙基）氨基丙基氨基）吖啶二盐酸盐（ICR-191）和1,3,7-丙二胺-N-（2-氯乙基）-N'-（6-氯-2-甲氧基-9-吖啶基）-N-乙基二盐酸盐（ICR-170）为例）的诱变作用，但对脂肪族诱变剂（以氮芥为例）则无此作用。生物物理研究表明，咖啡因和己酮可可碱可以与上述芳香族试剂形成堆积复合物。分子建模也证实了所研究分子之间存在堆积相互作用的可能性。
