Radiosensitizing and cytotoxic properties of ortho-substituted 4- and 5-nitroimidazoles: role of NPSH reactivity

Journal Article · Sun Feb 28 23:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90649-6· OSTI ID:6702914

Astor, M ^[1]; Hall, E J; Martin, J; Flynn, M; Biaglow, J; Parham, J C

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1. Columbia Univ. Coll. of Physicians and Surgeons, New York, NY

Chinese hamster (V79) cells were used to investigate the radiosensitizing efficiency and chemical reactivity with non-protein sulfhydryl (NPSH) compounds such as glutathione, for a series of sigma-substituted 4 and 5 nitroimidazoles. When added to cells 5 minutes prior to irradiation, MJL-1-191-VII (1-methyl-5-sulfonamide-4-nitroimidazole) sensitizes hypoxic cells commensurate with its electron affinity, while not affecting the radiosensitivity of aerated cells. If the drug is incubated with the cells for a period of time at 37/sub 0/C prior to irradiation, both aerated and hypoxic cells show an increase in radiosensitivity. Under these conditions the radiosensitizing effectiveness towards hypoxic cells appears to be particularly anomalous, inasmuch as enhancement ratios similar to misonidazole can be obtained at concentrations 50 to 100 times lower. The isomer SK-21981 (1-methyl-4-sulfonamide-5-nitroimidazole) does not behave in this anomalous way, but sensitizes to an extent predictable from its electron affinity. These compounds differ in the rate at which they react spontaneously and intracellularly with NPSH compounds such as glutathione. It is suggested that MJL sensitizes by two mechanisms; the first a function of its electron affinity and the second a function of its rapid reaction with endogenous radioprotective and chemotherapeutic compounds in the cell.

• OSTI ID: 6702914
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560121 -- Radiation Effects on Cells-- External Source-- (-1987)
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFFINITY
ANIMAL CELLS
ANIMALS
AZOLES
BIOCHEMISTRY
CELL CULTURES
CHEMICAL REACTIONS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DRUGS
FIBROBLASTS
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
THIOLS
TOXICITY
VERTEBRATES