Bleomycin-iron complexes and DNA radiation damage.
Radiation in the form of high-energy electrons dose-dependently activates bleomycin-Fe3+ in oxygen-containing DNA solutions. This activation causes a DNA fragmentation and a release of oxidative degradation products from the DNA. During irradiation, bleomycin-chelated Fe3+ is reduced to Fe2+. The kinetics of DNA base propenal-formation (measured by reaction with thiobarbituric acid) and iron-reduction (measured by bathophenanthroline chelation) are similar, with a yield of 1 mol base propenal/6 mol Fe3+ reduced. The activation of bleomycin-Fe3+ by irradiation could be instrumental in the synergistic action of radiotherapy and bleomycin observed on simultaneous administration in vivo.
Nørskov-Lauritsen
N
N
Danish Cancer Society, Department of Virus and Cancer, Arhus.
Ebbesen
P
P
Demant
E J
EJ
Christensen
J M
JM
D001761:Bleomycin / Q000737:chemistry / Q000528:radiation effects* / Q000031:analogs & derivatives; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004492:Edetic Acid; D004587:Electrophoresis, Agar Gel; D010084:Oxidation-Reduction
C023503:iron bleomycin; D001761:Bleomycin; D004247:DNA; D004492:Edetic Acid