APPROACHES FOR COMBINED RADIATION AND CHEMOTHERAPY
Experimental data are reported showing the synergistic injurious effects of radiation and metabolic inhibitors on tumor cells, and application of the principle to clinical problems of tumor therapy is described. In vitro studies were conducted with mammalian cell cultures treated with the fluorinated pyrimidine analogues, fluorouracil, and 5fluorodeoxyuridine, which are not incorporated but act as inhibitors of de novo thymidylic acid synthesis, preventing the conversion of uracil to thymine and thus interrupting DNA anabolism. Fluorouracil changed the slope of the x-ray dose-log survival curve when the drug was present in the medium throughout the period of incubation following irradiation. This was interpreted as potentiation by virtue of inhibition of the repair of DNA damaged by irradiation. It was also demonstrated that, in the in vitro system with hamster ovary cells, considerable radio- sensitization occurred when the cells were pretreated with 5-bromodeoxycytidine. The x-ray dose-log survival curve for hamster cells grown prior to irradiation for 5 days with 10/sup -4/ and 10/sup -3/M 5-bromodeoxycytidine showed that at 10/ sup -4/M the slope ratio is 1.74, while at 10/sup -3/M it is 2.56. Pretreatment of the hamster cells with 5-bromodeoxycytidine produced a higher degree of sensitization than pretreatment with either 5-bromodeoxyuridine or 5- iododeoxyuridine. A further increase in radiosensitization was shown when the cells were incubated with both 5-fluorouracil and 5-bromodeoxycytidine prior to irradiation. Although radiosensitization can be clearly demonstrated in vitro for many purine and pyrimidine analogues, their therapeutic exploitation remains to be demonstrated. Treatment of 5 cancer patients with x rays and chemotherapeutic agents is described; in each case the radiation effect was enhanced by the drug used, although tumor regression was not complete. (TCO)
- Research Organization:
- Stanford Univ., Calif.
- NSA Number:
- NSA-17-028613
- OSTI ID:
- 4702881
- Journal Information:
- Laval Medical (Canada), Vol. Vol: 34; Other Information: From Symposium on Radiosensitivity, Laval Univ., Quebec, Sept. 1962. Orig. Receipt Date: 31-DEC-63
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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