Radiosensitization of two murine fibrosarcomas with 6-thioguanine.
In Vivo murine tumor experiments were carried out to determine whether 6-thioguanine (6-TG) could enhance the cytotoxic effects of radiation on tumors. The combined effects of single and fractionated x-irradiation were evaluated on the transplanted methylcholanthrene induced fibrosarcoma (Meth-A) in BALB/c mice, a moderately radioresponsive tumor and on the radiation induced fibrosarcoma (RIF) in C3H/He mice, a highly radioresistant tumor. The combined treatment of single administration of 6-TG (25 mg/kg) and of x-irradiation (20 Gy) on Meth-A tumors produced more than 90% tumor control, whereas the radiation alone resulted in less than 5% tumor control. The radiosensitizing effect by 6-TG was higher when the drug was administered either 1 to 8 hr prior to or 24 hr after x-irradiation. The dose modification factor of single dose 6-TG (10 mg/kg) is estimated to be 1.47 for Meth-A tumor and 1.25 for RIF tumor. The tumor control rates of fractionated irradiation alone and with concomitant 6-TG in Meth-A tumors were 14% and 59%, respectively. Based on the studies reported here and well documented pharmacokinetics in humans, it is suggested that combined radiation therapy and 6-TG may provide an enhanced therapeutic effect even in tumor varieties where the drug has no apparent anti-tumor activity on non-irradiated cells.
Kim
J H
JH
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, N.Y. 10021.
Alfieri
A A
AA
Kim
S H
SH
Hong
S S
SS
D000818:Animals; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005354:Fibrosarcoma / Q000188:drug therapy / Q000209:etiology / Q000532:radiotherapy*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013866:Thioguanine / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; D008748:Methylcholanthrene; D013866:Thioguanine