DNA base damage by beta-lactam, tetracycline, bacitracin and rifamycin antibacterial antibiotics.
Several antibacterial antibiotics have been shown to participate with transition metal ions in chemical reactions leading to the formation of reactive oxygen species. An important host defence mechanism for dealing with invading bacteria involves the production of reactive oxygen species, such as superoxide, hydrogen peroxide and hypochlorous acid, by phagocytic cells. The production of reactive oxygens by redox cycling antibacterial antibiotics has led us to suggest that a 'phagomimetic' contribution may also be made in vivo. Here we show that four structurally different antibacterial antibiotics, in the presence of added copper salt, bring about oxidative modification to bases in DNA detected using gas chromatography-mass spectrometry. The drug most damaging to DNA was rifamycin SV which was more active than a reference mixture of hydrogen peroxide and ascorbic acid.
Department of Anaesthesia and Intensive Care, Royal Brompton Hospital, London, U.K.
G J
GJ
Quinlan
J M
JM
Gutteridge
D001414:Bacitracin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D004318:Doxycycline / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D008712:Methicillin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012294:Rifamycins / Q000494:pharmacology*
D012294:Rifamycins; D001414:Bacitracin; D003300:Copper; D004247:DNA; C026461:bacitracin A; C023808:rifamycin SV; D004318:Doxycycline; D008712:Methicillin; C029892:cupric chloride