Free radical formation from the antineoplastic agent VP 16-213.
Free radical formation from VP 16-213 was studied by ESR spectroscopy. Incubation of VP 16-213 with the one-electron oxidators persulphate-ferrous, myeloperoxidase (MPO)/hydrogen peroxide and horseradish peroxidase (HRP)/hydrogen peroxide readily led to the formation of a free radical. The ESR spectra obtained in the last two cases, were in perfect accord with that of a product obtained by electrochemical oxidation of VP 16-213 at +550 mV. The half-life of the free radical in 1 mM Tris (pH 7.4), 0.1 M NaCl at 20 degrees C, was 257 +/- 4 s. The signal recorded on incubation with HRP/H2O2 or MPO/H2O2 did not disappear on addition of 0.3 - 1.2 mg/ml microsomal protein. From incubations with rat liver microsomes in the presence of NADPH, no ESR signals were obtained.
Van Maanen
J M
JM
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
De Ruiter
C
C
Kootstra
P R
PR
De Vries
J
J
Pinedo
H M
HM
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005047:Etoposide; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver; D051381:Rats
D005609:Free Radicals; D005047:Etoposide