Comparative DNA damage and repair induced by misonidazole, CB 1954 and RSU 1069.
We have studied the ability of CB 1954, misonidazole, and RSU 1069 to induce biologically relevant DNA damage in single- and double-stranded phi X174 DNA under oxic, anoxic, and anoxic reductive conditions using a double transfection technique. In addition, the ability of the three drugs to induce the SOS repair response in E. coli under the same conditions was measured. Whereas the relative order of DNA damage was RSU 1069 greater than CB 1954 greater than misonidazole the order in inducing SOS repair was RSU 1069 greater than misonidazole greater than CB 1954. Drug-induced damage by RSU 1069 involves enhanced damage by endonuclease III suggesting drug-induced pyrimidine damage. There appears to be no correlation between drug-induced damage and the degree of SOS repair induction. Thus it appears that enzymes other than, or in addition to, those of the SOS repair system are involved in the repair of DNA damage induced by these drugs.
Dale
L D
LD
Chemotherapy Research Unit, North East London Polytechnic, UK.
Widdick
D A
DA
Edwards
D I
DI
Biol
G I
GI
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D003090:Coliphages; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D004926:Escherichia coli; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D011838:Radiation-Sensitizing Agents; C100099:tretazicar; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole