Phosphate-group of DNA as a potential target for RSU-1069, a nitroimidazole-aziridine radiosensitizer

Journal Article · Tue Jul 01 04:00:00 EDT 1986 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(86)90258-0· OSTI ID:5072265

Silver, A R; O'Neill, P; Jenkins, T C; McNeil, S S

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), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 7; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560111* -- Radiation Effects on Biochemicals-- In Vitro-- (-1987)
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
ANTINEOPLASTIC DRUGS
AZOLES
CELL CONSTITUENTS
DNA
DNA ADDUCTS
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MISONIDAZOLE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLASMIDS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
STRAND BREAKS
TOXICITY