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.