Dose response of amifostine in protection of growth plate function from irradiation effects.
The dose-response radioprotectant effects of amifostine on rat growth plate have not been studied. The purpose is to examine the relative effects of varying doses of amifostine on functional damage to the Sprague-Dawley rat growth plate from a single fraction radiation exposure. Thirty-six weanling Sprague-Dawley rats underwent single dose 17.5 Gy radiation exposure to the right knee. The contralateral left limb served as the nonirradiated control. Six groups of six animals each received, 20 minutes before radiation exposure, intraperitoneally administered amifostine at the following doses: 0, 50, 100, 150, 200, and 250 mg/kg. Six weeks after treatment, the rats were euthanized and the lower limbs disarticulated, skeletonized, radiographed, and measured. Statistically significant dose-related differences were observed between amifostine dosage groups for mean right-side growth, growth-loss, and limb-length discrepancy. The mean right-side growth recovered by amifostine administration increased from 14% at 50 mg/kg to 57% at 250 mg/kg. Growth-loss and limb discrepency were significantly reduced in proportion to increasing amifostine doses. Despite these positive effects of amifostine, amifostine associated mortality was identifiable beginning at 200 mg/kg and increased rapidly thereafter. This report suggests a directly proportional relationship between amifostine dose and its protective effects on the growth plate. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 73-79 (2000).
Damron
T A
TA
Orthopedic Laboratories, Institute for Human Performance, State University of New York at Syracuse, Syracuse, New York 13210, USA. damront@sprynet.com
Spadaro
J A
JA
Margulies
B
B
Damron
L A
LA
D004999:Amifostine / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000254:growth & development; D006130:Growth Disorders / Q000209:etiology* / Q000517:prevention & control; D006132:Growth Plate / Q000528:radiation effects*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000254:growth & development; D014886:Weaning
D011837:Radiation-Protective Agents; D004999:Amifostine