Our previous studies revealed that injury to the ciliated cells of the eustachian tube may be the primary cause of irradiation-induced serous otitis media. The purpose of this study was to investigate the effects of the radioprotector WR2721 on irradiation-induced injury to ciliated cells of the eustachian tube (ET) in chinchillas. Twelve chinchillas were divided into two groups: the control group and the experimental group, which was pretreated with a single intraperitoneal dose of the radioprotector S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR2721) 400 mg/kg. The two groups were exposed to 30 Gy of 13-MeV electrons in a single fraction to the area of the bullae and nasopharynx. Ciliary dysfunction was tested and ciliated cells of the ET were examined by scanning and transmission electron microscopy. Pretreatment with WR2721 was found to protect ciliated cells of the ET from irradiation injury.
OhashiYNakaiYIkeokaHEsakiYKoshimoHOnoyamaY. Mucosal pathology of an experimental otitis media with effusion after x-ray irradiation. Am J Otolaryngol1987; 8: 223–35.
9.
HonjoIOkazakiNNozoeTUshiroKKumazawaT. Experimental study of the pumping function of the eustachian tube. Acta Otolaryngol (Stockh)1981; 91: 85–9.
10.
NozoeTOkazakiNKodaYAyaniNKumazawaT. Fluid clearance of the eustachian tube. In: LimDJBluestoneCDKleinJONelsonJD, eds. Recent advances in otitis media with effusion. Philadelphia, Pa: BC Decker, 1984: 66–8.
11.
SigdestadCPGrdinaDJConnorAMHansonWR. A comparison of radioprotection from three neutron sources and 60Co by WR-2721 and WR-151327. Radiat Res1986; 106: 224–33.
12.
YuhasJM. Protective drugs in cancer therapy: optimal clinical testing and future directions. Int J Radiat Oncol Biol Phys1982; 8: 513–7.
13.
PhillipsTLKaneLUtleyJF. Radioprotection of tumor and normal tissues by thiophosphate compounds. Cancer1973; 32: 528–34.
14.
PhillipsTLWassermanTH. Promise of radiosensitizers and radioprotectors in the treatment of human cancer. Cancer Treat Rep1984; 68: 291–302.
15.
BogoVJacobsAJWeissJF. Behavioral toxicity and efficacy of WR-2721 as a radioprotectant. Radiat Res1985; 104: 182–90.
16.
YuhasJMStorerJB. Differential chemoprotection of normal and malignant tissues, J Natl Cancer Inst1969; 42: 331–5.
17.
YuhasJM. Biological factors affecting the radioprotective efficiency of S-2-[3-aminopropylamino] ethylphosphorothioic acid (WR2721), LD50(30) doses. Radiat Res1970; 44: 621–8.
18.
YuhasJMPhillipsTL. Pharmacokinetics and mechanism of action of WR2721 and other protective agents. In: NygaardOSimicM, eds. Radioprotectors and anticarcinogens. New York, NY: Academic Press, 1983: 639–53.
19.
RaseyJSKrohnKAMageeSMelsonNLayC. Comparison of the protective effects of three phosphorothioate radioprotectors in the RIF-1 tumor. Radiat Res1986; 108: 167–75.
20.
RaseyJSKrohnKAMenardTWSpenceAM. Comparative biodistribution and radioprotection studies with three radioprotective drugs in mouse tumors. Int J Radiat Oncol Biol Phys1986; 12: 1487–90.
21.
UtleyJFMarloweCWaddellWJ. Distribution of 35Slabeled WR2721 in normal and malignant tissues of the mouse. Radiat Res1976; 68: 284–91.
22.
WashburnLCCarltonJEHayesRL. Distribution of WR2721 in normal and malignant tissues of mice and rats bearing solid tumors: dependence on tumor type, drug dose and species. Radiat Res1974; 59: 475–83.
23.
YuhasJM. Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res1980; 40: 1519–24.
24.
MilasLHunterNItoHTravisELPetersLJ. Factors influencing radioprotection of tumors by WR2721. In: NygaardOSimicM, eds. Radioprotectors and anticarcinogens. New York, NY: Academic Press, 1983: 695–718.
25.
DonaldsonSSMoskowitzPSEvansJWFajardoLF. Protection from radiation nephropathy by WR2721. Radiat Res1984; 97: 414–23.
26.
JungTTKPennerGWeeksD. Ciliary abnormality of eustachian tube in the pathogenesis of radiation-induced otitis media. Abstracts of the Twelfth Midwinter Meeting, St Petersburg, Fla: Association for Research in Otolaryngology, 1989: 285.
27.
RaseyJSNelsonNJMahlerPAndersonKKrohnKAMenardT. Radioprotection of normal tissues against gamma rays and cyclotron neutrons with WR2721: LD50 studies and 35S-WR2721 biodistribution. Radiat Res1984; 97: 598–607.
28.
BakaletzLOGriffithSRLimDJ. Effect of prostaglandin E2 and bacterial endotoxin on the rate of dye transport in the chinchilla eustachian tube. In: LimDJBluestoneCDKleinJONelsonJD. Recent advances in otitis media. Toronto, Canada: BC Decker, 1988: 99–102.
