Inactivation and repair of double-stranded DNA damaged by the aziridinyl nitroimidazole RSU 1069.
Incubation of RSU 1069 in the presence of biologically active double-stranded phi X174 DNA resulted in, depending on pH, ionic strength and concentration of drug, inactivation of the DNA. A variety of lesions are induced including a high number of single-strand breaks and alkali-labile lesions, which are at most partly lethal. The main inactivating damage consists probably of base damage, induced by alkylation. A considerable part of the damage induced by RSU 1069 can be repaired by the various repair enzymes of the bacterial host of the phi X174 DNA. Finally the damage (pattern) depends considerably on the ionic composition of the reaction solution, which can be explained by an equilibrium model presented in this paper.
Lafleur
M V
MV
Department of Biophysics, Vrije Universiteit, Amsterdam, The Netherlands.
Westmijze
E J
EJ
Visser
O J
OJ
Wagenaar
N
N
Soetekouw
R
R
Loman
H
H
Retel
J
J
D000468:Alkalies; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D010584:Bacteriophage phi X 174 / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004279:DNA, Viral / Q000187:drug effects*; D004573:Electrolytes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000633:toxicity*
D000468:Alkalies; D000970:Antineoplastic Agents; D004279:DNA, Viral; D004573:Electrolytes; D011838:Radiation-Sensitizing Agents; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D004247:DNA; C069174:RSU 1137