Alleviation of mutagenic effects of polycyclic aromatic agents (quinacrine mustard, ICR-191 and ICR-170) by caffeine and pentoxifylline.
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.
Piosik
Jacek
J
Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kladki 24, 80-822 Gdańsk, Poland.
Ulanowska
Katarzyna
K
Gwizdek-Wiśniewska
Anna
A
Czyz
Agata
A
Kapuściński
Jan
J
Wegrzyn
Grzegorz
G
D000585:Aminacrine / Q000031:analogs & derivatives* / Q000633:toxicity; D000609:Aminoacridines / Q000633:toxicity; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D008958:Models, Molecular; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000494:pharmacology*; D009588:Nitrogen Mustard Compounds / Q000633:toxicity; D010431:Pentoxifylline / Q000494:pharmacology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011797:Quinacrine Mustard / Q000633:toxicity; D014733:Vibrio / Q000187:drug effects / Q000235:genetics
D000609:Aminoacridines; D016587:Antimutagenic Agents; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D011084:Polycyclic Aromatic Hydrocarbons; C091910:acridine mustard; D002110:Caffeine; D011797:Quinacrine Mustard; D000585:Aminacrine; C004294:acridine half-mustard; D010431:Pentoxifylline