Cytotoxicity and genotoxicity induced by the photochemical alkoxyl radical source N-tert-butoxypyridine-2-thione in L5178Y mouse lymphoma cells under UVA irradiation.
The cell-damaging effects of N-tert-butoxypyridine-2-thione (tBuOPT), which generates alkoxyl and thiyl radicals on photolysis, have been investigated in L5178Y mouse lymphoma cells. The UVA irradiation of 2.5 microM tBuOPT inhibits strongly cell growth and cell viability, causes pronounced membrane damage, and induces micronuclei. Without irradiation, tBuOPT does not cause any cell damage at 2.5 microM concentration. The phototoxicity of tBuOPT is effectively inhibited by the radical scavenger glutathione, while the photogenotoxicity (micronuclei induction) is not affected by this strong hydrogen-atom donor. Thus, for the cytotoxicity and genotoxicity different reactive species seems to be responsible. The cytotoxicity is presumably caused by oxyl radicals, which are derived from tert-butoxyl radicals generated by photocleavage of tBuOPT, while in the genotoxicity the less reactive pyridyl-2-thiyl radicals appear to play a role. These results demonstrate that N-alkoxypyridinethiones are useful photochemical sources of oxyl and thiyl radicals to elucidate biological effects caused by these free radicals.
Möller
Marianne
M
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacherstrasse 9, D-97078 Würzburg, Germany.
Adam
Waldemar
W
Marquardt
Stefan
S
Saha-Möller
Chantu R
CR
Stopper
Helga
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003624:Darkness; D005609:Free Radicals / Q000633:toxicity; D005978:Glutathione / Q000494:pharmacology; D007940:Leukemia L5178; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D011725:Pyridines / Q000737:chemistry / Q000633:toxicity*; D013871:Thiones / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D005609:Free Radicals; C110288:N-tert-butoxypyridine-2-thione; D011725:Pyridines; D013871:Thiones; D005978:Glutathione