Photoinduced reactions of anthraquinone antitumor agents with peptides and nucleic acid bases: an electron spin resonance and spin trapping study.
The photoexcitation (lambda = 313 +/- 10 nm) of adriamycin, daunomycin, and mitoxantrone in the presence of peptides or pyrimidine nucleic acid bases was investigated. In air-saturated and air-free solutions, peptides are decarboxylated by the photoexcited drug molecules. The decarboxylation reactions were shown to occur specifically at the C-terminal amino acid of the peptide. The decarboxylated peptide radicals were spin-trapped using 2-methyl-2-nitrosopropane (MNP) and identified by electron spin resonance (ESR). In air-free solutions, nucleic acid bases are oxidized by the photoexcited drug molecules predominantly generating C(5)-carbon-centered radicals in the pyrimidine rings of uracil, cytosine, and thymine. However, spin adducts of MNP and thymine were also obtained at the N(1) or N(3) positions of the pyrimidine ring. In air-saturated adriamycin and daunomycin solutions, the spin adducts of MNP with uracil or thymine are similar to those obtained following hydroxyl radical reactions with these pyrimidines. This suggests that in the presence of oxygen, the photoexcited adriamycin and daunomycin transfer an electron to oxygen generating the superoxide anion radicals (O2-.), which are precursors of hydroxyl radicals. O2-. was also formed when O2-saturated DNA solutions were photoirradiated (lambda = 313 +/- 10 and 438 +/- 10 nm) in the presence of adriamycin and daunomycin, indicating that the photodegradation of DNA in the presence of these drugs caused by hydroxyl radicals is mediated by dissolved oxygen.
Carmichael
A J
AJ
Riesz
P
P
D000880:Anthraquinones / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects; D003630:Daunorubicin / Q000528:radiation effects*; D003653:Decarboxylation; D004317:Doxorubicin / Q000528:radiation effects*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008942:Mitoxantrone; D009603:Nitroso Compounds; D010100:Oxygen; D010455:Peptides / Q000528:radiation effects*; D010777:Photochemistry; D011743:Pyrimidines / Q000528:radiation effects*; D012996:Solutions; D013113:Spin Labels
D000880:Anthraquinones; D005609:Free Radicals; D009603:Nitroso Compounds; D010455:Peptides; D011743:Pyrimidines; D012996:Solutions; D013113:Spin Labels; D004317:Doxorubicin; D004247:DNA; D008942:Mitoxantrone; C034526:tert-nitrosobutane; D010100:Oxygen; D003630:Daunorubicin