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In vivo radiosensitization by diethyldithiocarbamate
1Department of Radiotherapy, Groote Schuur Hospital/University of Cape Town, South Africa.
Radiation Research
|December 1, 1988
Summary
Diethyldithiocarbamate (DDC) shows potential as a cancer treatment by inhibiting superoxide dismutase (SOD). Optimal radiosensitization occurred 2-4 hours post-injection, suggesting therapeutic potential warranting further investigation.
Area of Science:
- Oncology
- Radiation Biology
- Pharmacology
Background:
- Diethyldithiocarbamate (DDC) exhibits dual properties: radiosensitizing via superoxide dismutase (SOD) inhibition and radioprotective effects.
- Understanding the temporal activity of DDC is crucial for optimizing its therapeutic application in cancer treatment.
Purpose of the Study:
- To investigate the impact of DDC on SOD activity and tumor response to X-irradiation in a murine cancer model.
- To determine the optimal timing and dosage of DDC for radiosensitization.
Main Methods:
- Intratumoral administration of DDC (50-300 mg/kg) in 3-methylcholanthrene-induced tumors in BALB/c mice.
- Assessment of SOD activity up to 24 hours post-DDC administration.
- Tumor growth-delay assay evaluating response to 11 Gy X-rays administered at various times after DDC injection.
Main Results:
- Maximal SOD inhibition (8% of control) was observed 1 hour after 100 mg/kg DDC.
- Enhanced tumor growth delay (7.11 ± 1.76 days) occurred when irradiation was performed 2-4 hours after 50 mg/kg DDC.
- Tumor cure was observed with higher DDC doses (1-6 hours prior to irradiation), indicating a dose- and time-dependent effect.
Conclusions:
- DDC-induced radiosensitization is likely mediated by SOD inhibition.
- A critical time window exists for DDC administration to achieve radiosensitization; insufficient time may lead to a masking radioprotective effect.
- Further research into the therapeutic potential of DDC for human cancer patients is warranted.