Influence of heat on the intracellular uptake and radiosensitization of 2-nitroimidazole hypoxic cell sensitizers in vitro

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

OSTI ID:5428923

Brown, D M; Cohen, M S; Sagerman, R H; Gonzalez-Mendez, R; Hahn, G M; Brown, J M

The effect of elevated temperature (44 degrees) on the intracellular uptake of the 2-nitroimidazole hypoxic cell radiosensitizer, misonidazole (MIS), and analogues more hydrophilic than MIS was studied in Chinese hamster ovary cells. It was found that the intracellular uptake of these compounds which enter cells by restricted passive diffusion can be enhanced approximately 4-fold when incubated at 44 degrees compared to the uptake at 37 degrees. Peak intracellular uptake (expressed as the ratio of intracellular concentration to extracellular concentration) following incubation of cells in 2 mM MIS was 100% at 44 degrees but only 25% at 37 degrees. Furthermore, a short-term nonlethal heat pulse (44 degrees for 15 min) with MIS present caused a 2-fold enhancement in uptake which was sustained for an additional 45 min at 37 degrees. This same nonlethal heat pulse was found to induce a similar enhancement in uptake even when MIS was added at subsequent time intervals at 37 degrees. The heat pulse induced a time-related enhancement of uptake at 37 degrees which increased for 1 hr and persisted for at least 6 hr. Finally, in vitro radiosensitization studies of hypoxic Chinese hamster ovary cells showed that the nonlethal heat pulse of 44 degrees for 15 min could greatly enhance the sensitization by low concentrations (0.5 mM) of MIS added after heating due to increased intracellular concentrations of the drug. MIS (0.5 mM) alone achieved a radiosensitization enhancement ratio of 1.29 (compared to irradiated hypoxic cells alone), while the addition of the short-term heat pulse, which had only a minor effect itself, achieved an enhancement ratio of 1.78.

• Research Organization: Department of Radiology, Stanford University School of Medicine, California
• OSTI ID: 5428923
• Journal Information: Cancer Res.; (United States), Vol. 43:7
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
HYPERTHERMIA
RADIOSENSITIVITY EFFECTS
MISONIDAZOLE
UPTAKE
ANOXIA
CHO CELLS
IN VITRO
OXYGEN
TEMPERATURE EFFECTS
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
AZOLES
BODY TEMPERATURE
DRUGS
ELEMENTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIZERS
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560201 - Thermal Effects- Cells- (-1987)