Mutagenic activity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin, which can damage dopaminergic neurons. It causes symptoms resembling those observed in patients suffering from Parkinson's disease, and hence this toxin is widely used in studies on animal models of this disorder. Mutagenicity of MPTP was also reported by some authors, but results obtained by others suggested that this compound is not mutagenic. Interestingly, those contrasting results were based on the same assay (the Ames test). Therefore, we aimed to test MPTP mutagenicity by employing a recently developed Vibrio harveyi assay, which was demonstrated previously to be more sensitive than the Ames test, at least for some mutagens. We found that MPTP showed a significant mutagenic activity. Moreover, MPTP mutagenicity was attenuated by methylxanthines, compounds that are known to form complexes with aromatic mutagens.
Ulanowska
Katarzyna
K
Department of Molecular Biology, University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Wegrzyn
Grzegorz
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000737:chemistry / Q000494:pharmacology*; D000609:Aminoacridines / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002110:Caffeine / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D009152:Mutagenicity Tests; D009498:Neurotoxins; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010431:Pentoxifylline / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D013806:Theophylline / Q000627:therapeutic use; D014733:Vibrio / Q000187:drug effects*
D000609:Aminoacridines; D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000697:Central Nervous System Stimulants; D016166:Free Radical Scavengers; D009498:Neurotoxins; D009588:Nitrogen Mustard Compounds; D010726:Phosphodiesterase Inhibitors; C091910:acridine mustard; D002110:Caffeine; D004317:Doxorubicin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013806:Theophylline; D010431:Pentoxifylline