Photosensitive interaction of RSU 1069 with DNA.
RSU 1069 is a 2-nitroimidazole radiosensitizer with an aziridine-containing side chain. In light (360 nm) the absorbance maximum of the nitro group at 325 nm disappears, which is accompanied by expulsion of the nitro group as the nitrite ion. We suggest an intramolecular cyclization of the aziridine side chain and the C2 of the imidazole ring as a possible explanation. This photosensitive effect was used to determine separately the damage to DNA induced by the reduced nitro group and the alkylating property of the aziridine. The aziridine-induced DNA damage is maximized in the dark when the nitro group is either absent (electrolytically reduced prior to the addition of DNA) or non functional (unreduced). In the light, damage is reduced. Typical DNA damage includes helix disruption leading to single strand breaks and the release of thymidine. Alkaline filter elution studies show evidence only for strand breakage and none for cross-linking indicating the drug is capable of mono-functional alkylation only.
D001388:Aziridines / Q000633:toxicity*; D001389:Azirines / Q000633:toxicity*; D004247:DNA; D003624:Darkness; D008027:Light; D008920:Misonidazole / Q000031:analogs & derivatives*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*
D001388:Aziridines; D001389:Azirines; D011838:Radiation-Sensitizing Agents; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D004247:DNA