Spin traps: in vitro toxicity and stability of radical adducts.
We have evaluated the effects of DMPO, CMPO, EMPO, BMPO, and DEPMPO on functioning CHO cells and the stability of the radical adducts in the presence of cells. The potential toxic effects of the spin traps were measured by two estimates of cell viability (trypan blue exclusion and colony formation) and one of cell function (rate of oxygen consumption). We also studied the effects of the spin traps on colony formation in a second cell line, 9L tumor cells. Toxicity varied with the type of cell line and the parameter that was measured. In aqueous solutions the order of stability for all spin adducts was SO(3) > OH > CH(3), while in cell suspensions it was SO(3) > OH approximately CH(3). The radical adducts of the new spin traps have significantly increased stability as compared to DMPO. These results indicate that the new spin traps potentially offer increased stability of spin adducts in functioning cells. It also is clear that it is necessary to carry out appropriate studies of the stability and toxicity in the system that is to be studied for any particular use of these spin traps. It then should be feasible to select the spin trap(s) best suited for the proposed study.
Khan
Nadeem
N
Department of Diagnostic Radiology, EPR Center, Dartmouth Medical School, Hanover, NH 03755, USA.
Wilmot
Carmen M
CM
Rosen
Gerald M
GM
Demidenko
Eugene
E
Sun
Jie
J
Joseph
Joy
J
O'Hara
Julia
J
Kalyanaraman
B
B
Swartz
Harold M
HM
D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005609:Free Radicals; D006207:Half-Life; D007700:Kinetics; D010101:Oxygen Consumption; D051381:Rats; D013113:Spin Labels; D019097:Spin Trapping; D013447:Sulfites / Q000737:chemistry; D014343:Trypan Blue; D014407:Tumor Cells, Cultured
D003497:Cyclic N-Oxides; D005609:Free Radicals; D013113:Spin Labels; D013447:Sulfites; D014343:Trypan Blue