Low concentrations of nitroimidazoles: Effective radiosensitizers at low doses

Journal Article · Sat Apr 30 04:00:00 EDT 1994 · International Journal of Radiation Oncology, Biology and Physics; (United States)

DOI:https://doi.org/10.1016/0360-3016(94)90230-5· OSTI ID:6901191

Skov, K A; MacPhail, S ^[1]

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1. Cancer Research Centre, Vancouver, British Columbia (Canada)

There have been various reports that nitroimidazole radiosensitizers are less effective modifiers of radiation response in the clinically relevant x-ray dose regions (0-4 Gy) than they are at doses used in classical in vitro experiments. Studies at low concentrations of etanidazole led to questioning of this generalization, and the purpose was to further investigate low concentrations at low doses, using the microscopic location of cells to facilitate these experiments. The observations are compared with data on these drugs in the literature using other methods and systems. Survival of V79 cells after irradiation in hypoxia [+-] drug at various concentrations was assessed using the Cell Analyser (DMIPS) for low doses, in comparison with the standard clonogenic assay (higher doses). Enhancement ratios (ERs) were calculated at 80% and 2% survival, respectively. Etanidazole (SR-2508) consistently gave higher ERs at low doses (measured at 80% survival) than at high doses (survival 2%), when cells were exposed to drug concentrations below [approximately]2 mM (e.g., at 1 mM, ER[sub 80%] = 2.2, ER[sub 2%] = 1.8 in CHO cells after 1 h preincubation at 37[degrees]C). Preincubation of cells for 1 h or 15 min at 37[degrees]C with etanidazole prior to irradiation increased the ERs at high and low doses but did not change the [open quotes]cross-over[close quotes] behavior (ER[sub 80%] > ER[sub 2%] at low concentrations, ER[sub 2%] > ER[sub 80%] above 2 mM), regardless of pretreatment at 37[degrees]C or cell line, (CHO and V79 cells), whereas the 5-nitroimidazole nimorazole consistently gave the same ERs whether determined at high or low radiation doses (e.g., at 1 mM, 1 h preincubation at 37[degrees]C ER[sub 80%] = ER[sub 2%] = 1.3). This crossover behavior also occurred after irradiation/preincubation at 0[degrees]C. The 2-nitroimidazole predecessor, misonadazole, shows the same cross-over behavior. 39 refs., 1 fig., 4 tabs.

• OSTI ID: 6901191
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 29:1; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AZOLES
COMPARATIVE EVALUATIONS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EVALUATION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PERFORMANCE TESTING
RADIOSENSITIZERS
TESTING