Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

Journal Article · Fri Jul 01 04:00:00 EDT 1983 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3576084· OSTI ID:5605007

Wright, J; Frank, L R; Bush, D; Harrison, G H

Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit.

• Research Organization: Department of Medicinal Chemistry/Pharmacognosy, University of Maryland, Baltimore
• OSTI ID: 5605007
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 95:1; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANOXIA
AZOLES
BACTERIA
BODY
CARCINOMAS
DISEASES
GLANDS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
MAMMARY GLANDS
MEMBRANE TRANSPORT
MICE
MICROORGANISMS
NEOPLASMS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN ENHANCEMENT RATIO
RADIOSENSITIVITY EFFECTS
RODENTS
SERRATIA
STRUCTURE-ACTIVITY RELATIONSHIPS
SURVIVAL CURVES
TOXICITY
VERTEBRATES