Objective: To investigate the early protective effects of amifostine against radiation-induced damage on rat testis tissue. Methods: Eighty adult male Wistar rats were randomized to 4 groups: Saline solution was given to group A for control, 200 mg/kg amifostine (WR-2721) to group B, a single fraction of 6 Gy local irradiation to testes in group C and 200 mg/kg amifostine 15–30 min before 6 Gy testicular irradiation to group D. Animals were sacrificed 3 weeks after treatment and their testes were removed for macroscopic, microscopic and ultrastructural histopathological examination. Results: The weights, widths and lengths of testes in the last 3 groups had decreased significantly when compared with the control group, but the decrease in widths after irradiation was found to be significantly less only in the amifostine plus radiation group. There was a significant reduction of testis weights in relation to the individual body weights in the irradiated testes compared with the other groups (p < 0.005), while there was no significant change of testis weight/total body weight ratio in amifostine plus irradiation group. Spermatogonium A and primary spermatocyte counts were also less in the treatment groups, and primary spermatocyte numbers were significantly higher in amifostine plus radiation group when compared with radiation alone group (p < 0.005). Pretreatment with amifostine reduced the decrease of primary spermatocyte counts by a factor of 1.28. Electron microscopic analysis did not show any cytotoxic effect of amifostine alone, and furthermore, ultrastructural findings were normal with the addition of amifostine prior to irradiation, though there was damage in the radiation exposure group. Conclusion: Amifostine when given alone by itself appears to cause adverse alterations in testis tissue; however, it has a radioprotective effect on spermiogenetic cells when used prior to radiation.

Links M, Lewis C: Chemoprotectants: A review of their clinical pharmacology and therapeutic efficacy. Drugs 1999;57:293–308.
Peters GJ, van der Vijgh WJF: Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): Preclinical aspects. Eur J Cancer 1995;31:1–7.
Castiglione F, Dalla Mola A, Porcile G: Protection of normal tissues from radiation and cytotoxic therapy: The development of amifostine. Tumori 1999;85:85–91.
Yuhas JM, Storer JB: Differential chemoprotection of normal and malignant tissues. J Natl Cancer Inst 1969;42:331–335.
Ito H, Meistrich ML, Barkley HT, et al: Protection of acute and late radiation damage of the gastrointestinal tract by WR-2721. Int J Radiat Oncol Biol Phys 1986;12:211–219.
Pratt NE, Sodicoff M: Morphological effects of WR-2721 on the rat parotid acinar cell. Radiat Res 1978;75:327–335.
Sodicoff M, Conger AD, Trepper B, et al: Short-term radioprotective effects of WR-2721 on the rat parotid glands. Radiat Res 1978;75:317–326.
Pratt NE, Sodicoff M, Liss J, et al: Radioprotection of the rat gland by WR-2721: Morphology at 60 days post-irradiation. Int J Radiat Oncol Biol Phys 1980;6:431–435.
Menard TW, Izutsu KT, Ensign WY, et al: Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: Effect on gland weight and secretion at 8–10 days postirradiation. Int J Radiat Oncol Biol Phys 1984;10:1555–1559.
Williams MV, Denekamp J: Modification of the radiation response of the mouse kidney by misonidazole and WR-2721. Int J Radiat Oncol Biol Phys 1983;9:1731–1736.
Travis EL, Fang MZ, Basic I: Protection of mouse bone marrow by WR-2721 after fractionated irradiation. Int J Radiat Oncol Biol Phys 1988;15:377–382.
Benova D: Antimutagenic properties of WR-2721 and of a radioprotective mixture, ATP-AET-serotonin, with regard to X-ray induced reciprocal translocations in mouse spermatogonia. Int J Radiat Oncol Biol Phys 1987;13:117–119.
Meistrich MI, Finch MV, Hunter N, et al: Protection of spermatogonial survival and testicular function by WR-2721 against high and low doses of radiation. Int J Radiat Oncol Biol Phys 1984;10:2099–2107.
Stewart FA, Rojas A: Radioprotection of mouse skin by WR-2721 in single and fractionated treatments. Br J Radiol 1982;55:42–47.
Hunter NR, Guttenberger R, Milas L: Modification of radiation-induced carcinogenesis in mice by misonidazole and WR-2721. Int J Radiat Oncol Biol Phys 1992;22:795–798.
Travis EL, Newman RA, Helbing SJ: WR-2721 modification of type II cell and endothelial cell function in mouse lung after single doses of radiation. Int J Radiat Oncol Biol Phys 1987;13:1355–1359.
Meistrich MI, Finch MV, Hunter N, et al: Cytotoxic effects of WR-2721 on mouse testicular cells. Int J Radiat Oncol Biol Phys 1984;10:1551–1554.
Johnsen SG: Testicular biopsy score count – A method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones 1970;1:2–25.
Aslam I, Fishel S, Moore H, et al: Fertility preservation of boys undergoing anti-cancer therapy: A review of the existing situation and prospects for the future. Hum Reprod 2000;15:2154–2159.
Schrader M, Heicappel S, Muller M, et al: Impact of chemotherapy on male fertility. Onkologie 2001;24:326–330.
Kuczyk M, Machtens S, Bokemeyer C, et al: Sexual function and fertility after treatment of testicular cancer. Curr Opin Urol 2000;10:473–477.
Puscheck E, Philip PA, Jeyendran RS: Male fertility preservation and cancer treatment. Cancer Treat Rev 2004;30:173–180.
Littley MD, Shalet SM, Morgenstern GR, et al: Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. Q J Med 1991;78:265–274.
Shafford EA, Kingston JE, Malpas JS, et al: Testicular function following the treatment of Hodgkin’s disease in childhood. Br J Cancer 1993;68:1199–1204.
Brougham MF, Kelnar CJ, Sharpe RM, et al: Male fertility following childhood cancer: Current concepts and future therapies. Asian J Androl 2003;5:325–337.
Ben Arush MW, Solt I, Lightman A, et al: Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymphoma. Pediatr Hematol Oncol 2000;17:239–245.
Colpi GM, Contalbi GF, Nerva F, et al: Testicular function following chemo-radiotherapy. Eur J Obstet Gynecol Reprod Biol 2004;113(suppl 1):S2–S6.
Pacini F, Gasperi M, Fugazzola L, et al: Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine. J Nucl Med 1994;35:1418–1422.
Hyer S, Vini L, O’Connell M, et al: Testicular dose and fertility in men following I(131) therapy for thyroid cancer. Clin Endocrinol (Oxf) 2002;56:755–758.
Wichers M, Benz E, Palmedo H, et al: Testicular function after radioiodine therapy for thyroid carcinoma. Eur J Nucl Med 2000;27:503–507.
Piroth MD, Hensley F, Wannenmacher M, et al: Male gonadal dose in adjuvant 3-d-pelvic irradiation after anterior resection of rectal cancer. Influence to fertility. Strahlenther Onkol 2003;179:754–759.
Huyghe E, Matsuda T, Daudin M, et al: Fertility after testicular cancer treatments: Results of a large multicenter study. Cancer 2004;100:732–737.
Malas S, Levin V, Sur RK, et al: Fertility in patients treated with radiotherapy following orchidectomy for testicular seminoma. Clin Oncol (R Coll Radiol) 1994;6:377–380.
Centola GM, Keller JW, Henzler M, et al: Effect of low dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J Androl 1994;15:608–612.
Shapiro E, Kinsella TJ, Makuch RW, et al: Effects of fractionated irradiation of endocrine aspects of testicular function. J Clin Oncol 1985;3:1232–1239.
Herrmann T: Radiation reactions in the gonads: Importance in patient counseling. Strahlenther Onkol 1997;173:493–501.
Naysmith TE, Blake DA, Harvey VJ, et al: Do men undergoing sterilizing cancer treatments have a fertile future? Hum Reprod 1998;13:3250–3255.
Budgell GJ, Cowan RA, Hounsell AR: Prediction of scattered dose to the testes in abdominopelvic radiotherapy. Clin Oncol (R Coll Radiol) 2001;13:120–125.
Beckham WA: Secondary electron scatter in radiotherapy: Implications for treatment fields in proximity to the lens of the eye and the testes. Phys Med Biol 1993;38:1013–1018.
Jaimala, Bhartiya HC, Pareek BP: Effects of S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) on the sensitivity of mouse spermatogonia A to radiation. Acta Radiol Oncol 1984;23:65–68.
Jaimala: Inhibition of radiation induced changes in testicular RNA content by a thiophosphate. Radiobiol Radiother 1989;30:163–166.
Bhartiya HC, Jaimala: Inhibition of reduction in the testicular weight by WR-2721 in relation to the body weight after whole-body gamma irradiation (abstract). Strahlenther Onkol 1986;162:68–70.
Milas L, Hunter N, Reid BO: Protective effects of WR-2721 against radiation-induced injury of murine gut, testis, lung and lung tumor nodules. Int J Radiat Oncol Biol Phys 1982;8:535–538.
Milas L, Hunter N, Reid BO, et al: Protective effects of S-2(3-aminopropylamino) ethylphosphorothioic acid against radiation damage of normal tissues and a fibrosarcoma in mice. Cancer Res 1982;42:1888–1897.
Jahnukainen K, Hou M, Parvinen M, et al: Stage-specific inhibition of deoxyfibonucleic acid synthesis and induction of apoptosis by anthracyclines in cultured rat spermatogenic cells. Biol Reprod 2000;63:482–487.
Jahnukainen K, Jahnukainen T, Salmi TT, et al: Amifostine protects against early but not late toxic effects of doxorubicin in infant rats. Cancer Res 2001;61:6423–6427.
Rigatos SK, Stathopoulos GP, Dontas I, et al: Investigation of doxorubicin tissue toxicity: Does amifostine provide chemoprotection? An experimental study. Anticancer Res 2002;22:129–134.
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