Photosensitization by antitumor agents, 4. Anthrapyrazole-photosensitized formation of single strand-breaks in DNA.
Single-strand breaks can be introduced into PM2 closed-circular DNA upon illumination with blue light, in the presence of the anthrapyrazole antitumor agent, compound 1. Damage is observed already after 1 min of blue light illumination, and is significantly enhanced by the presence of electron donors such as NADH, ascorbic acid or Fe(III)/EDTA complex. The photosensitizing properties were not observed for anthrapyrazole analogues with one or more hydroxyl substituents in the chromophore of the drug. The inhibitory effects of sodium azide, methanol, mannitol, SOD, and catalase suggest an oxygen-dependent mechanism of strand-break production, probably involving hydroxyl radicals. However, a second mechanism involving drug molecules bound to the DNA is also indicated under anoxic conditions in the presence of NADH.
Hartley
J A
JA
Department of Chemistry, University of Alberta, Edmonton, Canada.
Reszka
K
K
Lown
J W
JW
D018943:Anthracyclines; D000880:Anthraquinones / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects* / Q000302:isolation & purification / Q000528:radiation effects; D004279:DNA, Viral; D004587:Electrophoresis, Agar Gel; D009690:Nucleic Acid Conformation / Q000187:drug effects / Q000528:radiation effects; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology
D018943:Anthracyclines; D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D010083:Oxidants, Photochemical; D011720:Pyrazoles; C055925:anthrapyrazole