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:5597799

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 LD/sub 50/ was estimated to be 125 to 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: Univ. of Maryland, Baltimore
• OSTI ID: 5597799
• 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

560131* -- Radiation Effects on Microorganisms-- Basic Studies-- (-1987)
560152 -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANOXIA
AZOLES
BACTERIA
BODY
CARCINOMAS
CELL KILLING
DISEASES
DOSES
ELECTROMAGNETIC RADIATION
EXPERIMENTAL NEOPLASMS
GLANDS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IONIZING RADIATIONS
LETHAL DOSES
MAMMALS
MAMMARY GLANDS
MICE
MICROORGANISMS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN ENHANCEMENT RATIO
PHARMACOLOGY
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
RODENTS
SERRATIA
SURVIVAL CURVES
VERTEBRATES
X RADIATION