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Effects of AQ4N and its reduction product on radiation-mediated DNA strand breakage.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 1999 Nov 15; Vol. 123 (1), pp. 1-10. - Publication Year :
- 1999
-
Abstract
- Supercoiled plasmid pBR322 DNA was irradiated in phosphate buffer by 60Co gamma-rays at a dose rate 19.26 Gy/min and total dose of 10 Gy in the presence of a bioreductive antitumour prodrug namely 1,4-bis [¿2-(dimethylamino-N-oxide)ethyl¿ amino] 5, 8-dihydroxyanthracene-9,10-dione (AQ4N) and its DNA affinic reduction product 1,4-bis[¿2(dimethylamino)ethyl¿ amino] 5,8-dihydroxyanthracene-9,10-dione (AQ4) under air and nitrogen. AQ4N and AQ4 were found to protect against radiation-induced plasmid single and double strand breakage as assessed by agarose gel electrophoresis. The differences between the two agents, and between atmospheres of air or nitrogen were negligible. It was also found that the protection efficiencies of the compounds were pH dependent and showed maximum protection at pH 6. These results indicate that protection of DNA by AQ4 and AQ4N against radiation damage is an indirect effect since both agents are equally effective despite major differences in their DNA affinity. It is likely that radiation-induced phosphate buffer radicals are intercepted by AQ4 and AQ4N in a pH-dependent process.
- Subjects :
- Anthraquinones metabolism
Antineoplastic Agents metabolism
DNA, Circular drug effects
DNA, Superhelical drug effects
Oxidation-Reduction
Plasmids radiation effects
Prodrugs metabolism
Anthraquinones pharmacology
Antineoplastic Agents pharmacology
DNA Damage
DNA, Circular radiation effects
DNA, Superhelical radiation effects
Prodrugs pharmacology
Radiation-Protective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0009-2797
- Volume :
- 123
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 10597898
- Full Text :
- https://doi.org/10.1016/s0009-2797(99)00097-6