Studies on single-strand scissions to cell-free plasmid DNA by the dopaminergic neurotoxin 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline).
The DNA-damaging effect of the potent dopaminergic neurotoxin 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) is reported. After irradiation (300 nm, 350 nm) of cell-free pBR322 DNA in the presence of TaClo, single-strand breaks were observed by gel electrophoresis. It seems likely that TaClo undergoes a light-induced formation of reactive species (probably radicals). In comparison with TaClo, the bromo derivative exhibits an increased toxic action while the fluoro derivative shows a weaker effect towards DNA. In the presence of Cu(II) at 37 degrees C in the dark, DNA strand scissions were found to occur, too. The formation of Cu(I), as detected by UV-absorption at 480 nm using the Cu(I) complexing ligand BCS, hints at the formation of a reactive species by a Cu(II)/Cu(I) mediated redox cycle. Until now, the chemical nature of this reactive species has not been elucidated.
Bringmann
G
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074, Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Münchbach
M
M
Feineis
D
D
Faulhaber
K
K
Ihmels
H
H
D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D002474:Cell-Free System; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000187:drug effects* / Q000502:physiology; D018807:Polymorphism, Single-Stranded Conformational
D002243:Carbolines; D009498:Neurotoxins; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D003300:Copper; D004247:DNA