Phosphate-group of DNA as a potential target for RSU-1069, a nitroimidazole-aziridine radiosensitizer
Strand breakage of plasmid DNA by parent and radiation-reduced RSU-1069 (2.0-8.0 mmol dm-3) has been measured in air over 4 hr at 310K. Reduced RSU-1069 was shown to be approximately 4 times as efficient as the parent compound at causing strand breakage. The aziridine moiety of both parent and reduced RSU-1069 is required for strand break production and, furthermore, is capable of alkylating inorganic phosphate (k = 1.0 X 10(-3) dm3 mol-1 s-1) and a series of nucleotides (k = 0.8 - 2.1 X 10(-3) dm3 mol-1 s-1) at pH 7.0. From the determined rate constants and the nature of the adducts observed, it was shown that phosphate is a target on nucleotides, although additional sites probably exist particularly, on dGMP and dAMP. The mechanism of action of RSU-1069 is discussed in terms of its ability to act as a cytotoxic agent, radiosensitizer and bioreductive drug.
- Research Organization:
- Medical Research Council, Chilton, England
- OSTI ID:
- 5072265
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 7
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA
STRAND BREAKS
IMIDAZOLES
RADIOSENSITIVITY EFFECTS
TOXICITY
ALKYLATING AGENTS
DNA ADDUCTS
MISONIDAZOLE
PLASMIDS
ADDUCTS
ANTINEOPLASTIC DRUGS
AZOLES
CELL CONSTITUENTS
DRUGS
HETEROCYCLIC COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIZERS
560111* - Radiation Effects on Biochemicals- In Vitro- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)