Increased tumor control rates in murine fibrosarcoma by combined therapy with L-alanosine and radiation.
L-Alanosine, an analog of L-aspartic acid, was investigated as one of a series of chemical compounds that may have inhibitory effects on the repair of potentially lethal damage caused by radiation using an in vivo murine fibrosarcoma (Meth-A tumor) in BALB/cBy male mice. The combined treatment of single administration of L-alanosine (600 mg/kg) and single dose of X-irradiation (20 Gy) on Meth-A tumors produced 62% tumor control, while the radiation alone resulted in less than 5% tumor control. The potentiating effect by L-alanosine was higher when the drug was administered 8 h prior to X-irradiation. The dose modification factor of the drug is estimated to be 1.4 for Meth-A tumor. The increased tumor control rates with combined alanosine and radiation were highly dependent upon the time and sequence of the combined treatment. The reason for reduced efficacy at treatment times of less than 8 h prior to X-irradiations appears to be related in part to the modulation of the body temperature by L-alanosine when combined with Ketamine, an anesthetic agent.
Hong
S S
SS
Radiotherapy Research Laboratory, Sloan-Kettering Institute, New York, New York 10021.
Alfieri
A A
AA
Kim
S H
SH
Kim
J H
JH
D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011838:Radiation-Sensitizing Agents
D000903:Antibiotics, Antineoplastic; D011838:Radiation-Sensitizing Agents; C000082:alanosine; D008748:Methylcholanthrene; D007649:Ketamine; D000409:Alanine