Toxicity of RSU-1069 for KHT cells treated in vivo or in vitro: evidence for a diffusible toxic product

Journal Article · Sat Apr 01 04:00:00 EST 1989 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(89)90928-0· OSTI ID:6074101

Hill, R P; Gulyas, S; Whitmore, G F

RSU-1069 is a highly effective hypoxic cell cytotoxin in KHT sarcomas treated in vivo. However, relative to the hypoxic cells, the oxic cells in the tumor appear more sensitive to the drug than would have been predicted on the basis of results with CHO (AA8-4) cells treated in vitro with the drug under oxic and hypoxic conditions. To examine possible reasons for this difference, suspensions of KHT cells were prepared from tumors growing in vivo, and treated with RSU-1069 in vitro under oxic or hypoxic conditions. The sensitivity of the KHT cells was similar to that of AA8-4 cells, regardless of whether the cells were obtained from untreated tumors or from tumors given 15 Gy in vivo just prior to the preparation of the cell suspension. We observed, however, that the sensitivity of both AA8-4 cells and KHT cells to drug treatment under hypoxic conditions increased with the density of the cells in the treated suspension. This result suggests the possibility that a diffusible toxic product may be released from cells. Such a product could contribute to the toxicity of the drug for oxic cells in tumors in situ.

• Research Organization: Ontario Cancer Institute, Toronto (Canada)
• OSTI ID: 6074101
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 16:4; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

550603 -- Medicine-- External Radiation in Therapy-- (1980-)
560120* -- Radiation Effects on Biochemicals
Cells
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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
CHO CELLS
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
MICE
MISONIDAZOLE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIZERS
RODENTS
SARCOMAS
SENSITIVITY
TOXICITY
TUMOR CELLS
VERTEBRATES