J Vet Sci.  2006 Mar;7(1):19-23. 10.4142/jvs.2006.7.1.19.

Histopathological changes of testes and eyes by neutron irradiation with boron compounds in mice

• Kim YJ
• Yoon WK
• Ryu SY
• Chun KJ
• Son HY
• Cho SW

• KMID: 1103548
• DOI: http://doi.org/10.4142/jvs.2006.7.1.19

Abstract

This study was performed to investigate the biological effects of boron neutron capture therapy (BNCT) on the testes and eyes in mice using HANARO Nuclear Reactor, Korea Atomic Energy Research Institute. BNCT relies on the high capacity of (10)B in capturing thermal neutrons. Sodium borocaptate (BSH, 75 ppm, iv) and boronophenylalanine (BPA, 750 ppm, ip) have been used as the boron delivery agents. Mice were irradiated with neutron (flux: 1.036739E +09, Fluence 9.600200E+12) by lying flat pose for 30 (10 Gy) or 100 min (33 Gy) with or without boron carrier treatment. In 45 days of irradiation, histopathological changes of the testes and eyes were examined. Thirty-three Gy neutron irradiation for 100 min induced testicular atrophy in which some of seminiferous tubules showed complete depletion of spermatogenic germ cells. Lens epithelial cells and lens fiber were swollen and showed granular changes in an exposure time dependent manner. However, boron carrier treatment had no significant effect on the lesions. These results suggest that the examination of histopathological changes of lens and testis can be used as "biological dosimeters" for gauging radiation responses and the HANARO Nuclear Reactor has sufficient capacities for the BNCT.

Keyword

boron; eye; histopathology; neutron irradiation; testes

MeSH Terms

Animals
Boranes/*pharmacology
Borohydrides/*pharmacology
Boron Neutron Capture Therapy/*methods
Eye/pathology/*radiation effects
Histocytochemistry
Male
Mice
Mice, Inbred C57BL
Neutrons
Phenylalanine/*analogs&derivatives/pharmacology
Seminiferous Tubules/pathology/*radiation effects
Specific Pathogen-Free Organisms
Sulfhydryl Compounds/*pharmacology

Figure

• 

  Fig. 1 Seminiferous tubules from the control mouse testis containing normal spermatogenic germ cells. H&E stain, ×200.

• 

  Fig. 2 Seminiferous tubules from the mouse irradiated with 33 Gy neutron for 100 min. Some tubules are lined Sertoli cells with a few germ cells. H&E stain, ×200.

• 

  Fig. 3 Seminiferous tubules from the mouse pretreated with boronophenylalanine and irradiated with 33 Gy neutron for 100 min. Seminiferous tubules are lined Sertoli cells with a few germ cells. H&E stain, ×200.

• 

  Fig. 4 Seminiferous tubules from the mouse pretreated with sodium borocaptate and irradiated with 33 Gy neutron for 100 min. Some seminiferous tubules are lined Sertoli cells with a few germ cells. H&E stain, ×200.

• 

  Fig. 5 Lens from the control mouse eye. Note the nucleated lens fibers below the single layer of cuboidal epithelium. H&E stain, ×400.

• 

  Fig. 6 Lens from the mouse irradiated with 33 Gy neutron for 100 min. Lens epithelial cells and lens fiber are swollen and showing granular changes H&E stain, ×400.

• 

  Fig. 7 Lens from the mouse pretreated with boronophenylalanine and irradiated with 33 Gy neutron for 100 min. Lens epithelial cells and lens fiber are swollen and showing granular changes and a few vacuoles are evident. H&E stain, ×400.

• 

  Fig. 8 Lens from the mouse pretreated with sodium borocaptate and irradiated with 33 Gy neutron for 100 min. Lens epithelial cells and lens fiber are swollen and showing granular changes and a few vacuoles are evident. H&E stain, ×400.

Reference

1. Barth RF, Soloway AH, Fairchild RG. Boron neutron capture therapy of cancer. Cancer Res. 1990. 50:1061–1070.

2. Barth RF, Soloway AH, Goodman JH, Gahbauer RA, Gupta N, Blue TE, Yang W, Tjarks W. Boron neutron capture therapy of brain tumors: an emerging therapeutic modality. Neurosurgery. 1999. 44:433–451.

3. Binns PJ, Riley KJ, Harling OK. Epithermal neutron beams for clinical studies of boron neutron capture therapy: a dosimetric comparison of seven beams. Radiat Res. 2005. 164:212–220.

4. Coderre JA, Elowitz EH, Chadha M, Bergland R, Capala J, Joel DD, Liu HB, Slatkin DN, Chanana AD. Boron neutron capture therapy for glioblastoma multiforme using p-boronophenyl alanine and epithermal neutrons: trial design and early clinical results. J Neurooncol. 1997. 33:141–152.

5. Coderre JA, Morris GM. The radiation biology of boron neutron capture therapy. Radiat Res. 1999. 151:1–18.

6. Coderre JA, Turcotte JC, Riley KJ, Binns PJ, Harling OK, Kiger WS 3rd. Boron neutron capture therapy: cellular targeting of high linear energy transfer radiation. Technol Cancer Res Treat. 2003. 2:355–375.

7. Dagrosa MA, Viaggi M, Rebagliati RJ, Castillo VA, Batistoni D, Cabrini RL, Castiglia S, Juvenal GJ, Pisarev MA. Biodistribution of p-borophenylalanine (BPA) in dogs with spontaneous undifferentiated thyroid carcinoma (UTC). Appl Radiat Isot. 2004. 61:911–915.

8. Hatanaka H. Karim ABMF, Law ER, editors. Boron-neutron capture therapy for tumors. Glioma. 1991. Berlin: Springer-Verlag;233–249.

9. Hatanaka H, Nakagawa Y. Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy. Int J Radiat Oncol Biol Phys. 1994. 28:1061–1066.

10. Hawthorne MF. New horizons for therapy based on the boron neutron capture reaction. Mol Med Today. 1998. 4:174–181.

11. Heine U, Klug H, Weber C, Eichhorn HJ, Welker K, Regel K. Ultrastructural retinal changes after irradiation with fast neutrons. Ophthalmic Res. 1987. 19:76–81.

12. Imahori Y, Ueda S, Ohmori Y, Yoshino E, Ono K, Kobayashi T, Takagaki M, Oda Y, Ido T, Mishima Y. Positron emission tomography and boron neutron capture therapy using bronophenylallanine for highgrade gliomas: Part II. Clin Cancer Res. 1998. 4:1833–1841.

13. Kinashi Y, Masunaga S, Ono K. Mutagenic effect of borocaptate sodium and boronophenylalanine in neutron capture therapy. Int J Radiat Oncol Biol Phys. 2002. 54:562–567.

14. Matalka KZ, Barth RF, Bailey MQ, Wilkie DA, Koestner AD, Hopewell JW. Radiation effects of Boron neutron capture therapy on brain, skin, and eye of rats. Int J Radiat Oncol Biol Phys. 1994. 28:1089–1097.

15. Mishima Y, Honda C, Ichihashi M, Obara H, Hiratsuka J, Fukuda H, Karashima H, Kobayashi T, Kanda K, Yoshino K. Treatment of malignant melanoma by single thermal neutron capture therapy with melanoma seeking 10B-compound. Lancet. 1989. 2:388–389.

16. Obayashi S, Kato I, Ono K, Masunaga S, Suzuki M, Nagata K, Sakurai Y, Yura Y. Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy. Oral Oncol. 2004. 40:474–482.

17. Soloway AH, Hatanaka H, Davis MA. Penetration of brain and brain tumor. VII. Tumor-binding sulfhydral boron compounds. J Med Chem. 1967. 10:714–717.

18. Son HY, Kim YB, Kang BH, Cho SW, Ha CS, Roh JK. Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat. Reprod Toxicol. 1999. 13:179–187.

19. Suzuki M, Masunaga SI, Kinashi Y, Takagaki M, Sakurai Y, Kobayashi T, Ono K. The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice. Jpn J Cancer Res. 2000. 91:1058–1064.

20. van Beek ME, Davids JA, de Rooij DG. Variation in the sensitivity of the mouse spermatogonial stem cell population to fission neutron irradiation during the cycle of the seminiferous epithelium. Radiat Res. 1986. 108:282–295.

21. Yang W, Barth RF, Rotaru JH, Boesel CP, Wilkie DA, Bresnahan JC, Hadjiconstantinou M, Goettl VM, Joel DD, Nawrocky MM. Boron neutron capture therapy of brain tumors: functional and neuropathologic effects of blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. J Neurooncol. 2000. 48:179–190.

22. Leśnikowski ZJ, Paradowska E, Olejniczak AB, Studzinska M, Seekamp P, Schubler U, Gabel D, Schinazi RF, Plesek J. Towards new boron carriers for boron neutron capture therapy: metallacarboranes and their nucleoside conjugates. Bioorg Med Chem. 2005. 13:4168–4417.