Halogenated pyrimidine sensitization of low dose rate irradiation in human malignant glioma

• Published in: International journal of radiation oncology, biology, physics Vol. 26; no. 4; pp. 637 - 642
• Main Authors: McLaughlin, Patrick W, Mancini, William R, Stetson, Phillip L, Greenberg, Harry S, Nguyen, Nguyen, Seabury, Heather, Heidorn, Doug B, Lawrence, Theodore S
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.07.1993; Elsevier
• Subjects: ANTIMETABOLITES; AZINES; Biological and medical sciences; Brd/Urd; Bromodeoxyuridine - therapeutic use; BROMOURACILS; BUDR; DISEASES; Dose-Response Relationship, Radiation; DRUGS; Glioma - radiotherapy; GLIOMAS; Halogenated pyrimidines; HETEROCYCLIC COMPOUNDS; Humans; HYDROXY COMPOUNDS; In Vitro Techniques; Low dose rate; Malignant glioma; Medical sciences; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; NUCLEOSIDES; NUCLEOTIDES; ORGANIC BROMINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PYRIMIDINES; Radiation sensitizers; Radiation therapy and radiosensitizing agent; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; Radiation-Sensitizing Agents - therapeutic use; RADIOLOGY; RADIOSENSITIVITY EFFECTS; RADIOTHERAPY; Radiotherapy Dosage; RIBOSIDES; Survival Rate; THERAPY; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - radiation effects; Tumors; URACILS 560120 > Radiation Effects on Biochemicals, Cells, & Tissue Culture; Low dose rate; Halogenated pyrimidines; Malignant glioma; Radiation sensitizers; Brd/Urd; Human; Cell culture; Nervous system diseases; Low dose; Malignant tumor; Radiotherapy; Dose rate; In vitro; Established cell line; Central nervous system disease; Halogen; Pyrimidine derivatives
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/0360-3016(93)90281-Y

Purpose : To determine the potential advantage of combining halogenated pyrimidine radiosensitization and continuous low dose rate irradiation in human malignant glioma. Methods and Materials : An established glioma line (U-251) was incubated with 5-bromo-2-doxyuridine (BrdUrd) at clinically achievable concentrations at three dose rates of interest-100 cGy/min (typical of external beam therapy), 43 cGy/hr (typical of temporary afterloaded implants), and 12 cGy/hr (typical of permanent implants). Results : After exposure to 1 pM BrdUrd, the greatest enhancement ratio was seen at the 12 cGy/hr dose rate, implying a BrdUrd induced inverse dose rate effect independent of a G2M block. Under these conditions, the mean inactivation dose after 1 μM BrdUrd exposure was equivalent for 100 cGy/min and 12 cGy/hr. Conclusion : These results support the use of halopyrimidines as sensitizers of temporary afterloaded and permanent implants.