Sensitizers, protectors and oncogenic transformation in vitro

Journal Article · Mon Mar 01 04:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90732-5· OSTI ID:6715054

Miller, R C; Osmak, R; Zimmerman, M; Hall, E J

Systems developed to assay oncogenic transformation in vitro represent a rapid and powerful tool to screen and compare new radiosensitizers in their carcinogenic potential, and to search for compounds that reduce or inhibit carcinogenesis produced by both radiation and sensitizers. An established line of mouse embryo fibroblasts (C3H/10T1/2 cells) has been used to determine the incidence of transformation produced by a variety of 2 and 5 substituted nitroimidazoles; these include metronidazole, desmethylmisonidazle, misonidazole, SR 2508, SR 2555, R0-07-0741, RSU-1047 and RSU-1021. Most of these sensitizers produce a similar level of transformation; for example a three day exposure of aerated cells to a concentration of 1 mM of the drug results in a transformation incidence comparable to 1 Gy of X rays. The notable exception is SR 2508 which produces a five-fold higher incidence of transformation. The potential carcinogenicity of sensitizers must be considered in choosing which of the currently available new drugs is to be used in clinical trials as an alternative to misonidazle. Superoxide dismutase (SOD), a known free radical scavenger, has been shown to reduce the level of transformation produced by radiation and sensitizers. To be effective, SOD must be present for prolonged periods during the fixation and expression period of the transformation process.

• Research Organization: Columbia Univ. Coll. of Physicians and Surgeons, New York, NY
• OSTI ID: 6715054
• 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.
ALCOHOLS
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
CARCINOGEN SCREENING
CONNECTIVE TISSUE CELLS
DRUGS
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
IN VITRO
MAMMALS
METRONIDAZOLE
MICE
MISONIDAZOLE
NITRO COMPOUNDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIZERS
RODENTS
SCREENING
SOMATIC CELLS
VERTEBRATES