DNA-Targeted 2-Nitroimidazoles: Studies of the Influence of the Phenanthridine-Linked Nitroimidazoles, 2-NLP-3 and 2-NLP-4, on DNA Damage Induced by Ionizing Radiation

Journal Article · Tue Jan 01 04:00:00 EST 2002 · Radiation Research

DOI:https://doi.org/10.1667/0033-7587(2002)158[0302:DTNSOT]2.0.CO;2· OSTI ID:15001586

Buchko, Garry W ^[1]; Weinfeld, Michael ^[2]

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1. BATTELLE (PACIFIC NW LAB)
2. Cross Cancer Institute

The nitroimidazole-linked phenanthridines 2-NLP-3 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and 2-NLP-4 (5-[3-(2-nitro-1-imidazoyl)-butyl1]-phenanthridinium bromide) are composed of the radiosensitizer, 2-nitroimidazole, attached to the DNA intercalator phenanthridine via a 3- and 4-carbon linker, respectively. Previous in vitro assays show both compounds to be 10 - 100 times more efficient as hypoxic cell radiosensitizer, misonidazole[Cowan et al., Radiat. Res. 127, 81-89, 1991]. Here we have used a 32P postlabeling assay and 5'-end labeled oligonucleotide assay to compare the radiogenic DNA damage generated in the presence of 2-NLP-3, 2-NLP-4 compared to irradiation in the presence of misonidazole. This may account, at least in part, for the greater cellular radiosensitization shown by the nitroimidazole-linked phenanthridines over misonidazole.

• Research Organization: Pacific Northwest National Lab., Richland, WA (US)
• Sponsoring Organization: US Department of Energy (US)
• DOE Contract Number: AC06-76RL01830
• OSTI ID: 15001586
• Report Number(s): PNWD-SA-5465
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 158
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA
DNA DAMAGES
IN VITRO
IONIZING RADIATIONS
IRRADIATION
MISONIDAZOLE
OLIGONUCLEOTIDES