Diethyldithiocarbamate enhancement of radiation and hyperthermic effects on Chinese hamster cells in vitro. [By inhibition of superoxide dismutase activity thus enhancing superoxide radical toxicity in the cells]
To test the possibility of enhancing O/sub 2/- toxicity during radiation therapy and/or hyperthermia, Chinese hamster cells (Don) were treated with the drug diethyldithiocarbamate (DDC) in vitro. This drug has been shown to inhibit, both in vitro and in vivo, the enzyme superoxide dismutase (SOD) which is responsible for eliminating the 0/sub 2/- radical in cells. We observed that the cytocidal effect of DDC on Don cells is dependent on both DDC concentration and exposure time. After 8 to 10 days of incubation with 10/sup -9/ M DDC, no change in cell survival was noted; however, incubation with 10/sup -4/ M DDC produced a marked loss in colony formation. When DDC-treated cells were ..gamma..-irradiated, they did not survive as well as cells that were treated with either radiation or DDC alone. The combined effects of hyperthermia and DDC were dramatic. Cells treated 5 min at 43/sup 0/C with 10/sup -4/ M DDC or 10 min at 43/sup 0/C with 10/sup -5/ M DDC showed significant decrease in survival. These results suggest that DDC may be a potentially powerful sensitizing agent in tumor therapy, since there is increasing evidence that tumor cells have a lower level of superoxide dismutase.
- Research Organization:
- Tufts-New England Medical Center, Boston, MA
- OSTI ID:
- 6082836
- Journal Information:
- Radiat. Res.; (United States), Vol. 77:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOLOGICAL RADIATION EFFECTS
DEDTC
RADIOSENSITIVITY EFFECTS
ENZYME ACTIVITY
INHIBITION
OXIDOREDUCTASES
CELL CULTURES
COLONY FORMATION
GAMMA RADIATION
HYPERTHERMIA
IRRADIATION
SUPEROXIDE RADICALS
SURVIVAL TIME
BIOLOGICAL EFFECTS
BODY TEMPERATURE
CARBAMATES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CHELATING AGENTS
ELECTROMAGNETIC RADIATION
ENZYMES
IONIZING RADIATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RADICALS
560121* - Radiation Effects on Cells- External Source- (-1987)
550200 - Biochemistry