Apoptotic cell death induced by low-dose radiation in male germ cells: Hormesis and adaptation

Critical Reviews in Toxicology

Volumn 37, Issue 7, 2007, Pages 587-605

  Liu, Guangwei ^a,b   Gong, Pingsheng ^a   Bernstein, Lori R ^c   Bi, Yujing ^d   Gong, Shouliang ^e   Cai, Lu ^a,e  

^a JILIN UNIVERSITY   (China)

^b INSTITUTE OF ZOOLOGY   (China)

^c TEXAS A AND M UNIVERSITY   (United States)

^d BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

^e University of Louisville School of Medicine   (United States)

Author keywords

Adaptive response; Apoptosis; Germ cells; Hormesis; Low dose radiation

Indexed keywords

APOPTOTIC PROTEASE ACTIVATING FACTOR 1; BH3 PROTEIN; CASPASE 3; CASPASE 9; CYTOCHROME C; FAS ANTIGEN; FAS ASSOCIATED DEATH DOMAIN PROTEIN; FAS LIGAND; GRANZYME B; INDUCIBLE NITRIC OXIDE SYNTHASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PROCASPASE 3; PROCASPASE 8; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN P53; SECOND MITOCHONDRIAL ACTIVATOR OF CASPASE;

ADAPTATION; ANTIOXIDANT ACTIVITY; APOPTOSIS; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL DIVISION; CELL MATURATION; CELL PROLIFERATION; DNA DAMAGE; DNA RECOMBINATION; GAMETE; GENETIC TRANSCRIPTION; GENOMICS; GERM CELL; HORMESIS; HUMAN; MALE; METABOLISM; NONHUMAN; PROTEIN FUNCTION; RADIATION DOSE; RADIATION EXPOSURE; RADIATION STERILIZATION; RADIOBIOLOGY; RADIOSENSITIVITY; REPRODUCTIVE TOXICITY; REVIEW; SIGNAL TRANSDUCTION; SPERMATOCYTE; SPERMATOGENESIS; SPERMATOGONIUM; TESTIS; WHOLE BODY RADIATION;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; APOPTOSIS; DOSE-RESPONSE RELATIONSHIP, RADIATION; MALE; MICE; RATS; SPERMATOZOA; TESTIS;

ANIMALIA;

EID: 34547668774     PISSN: 10408444     EISSN: 15476898     Source Type: Journal    
DOI: 10.1080/10408440701493061     Document Type: Review

References (102)

1. Allan, D.J., Harmon, B.V., and Roberts, S.A. (1992). Spermatogonial apoptosis has three morphologically recognizable phases and shows no circadian rhythm during normal spermatogenesis in the rat. Cell Prolif. 25:241-250.
2. Azzam, E.I., and Little, J.B. (2004). The radiation-induced bystander effect: evidence and significance. Hum. Exp. Toxicol. 23:61-65.
3. Bartke, A. (1995). Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon? Endocrinology 136:3-4.
4. Beumer, T.L., Roepers-Gajadien, H.L., Gademan, I.S., Lock, T.M., Kal, H.B., and De Rooij, D.G. (2000). Apoptosis regulation in the testis: Involvement of Bcl-2 family members. Mol. Reprod. Dev. 56:353-359.
5. Blanco-Rodriguez, J., and Martinez-Garcia, C. (1996). Spontaneous germ cell death in the testis of the adult rat takes the form of apoptosis: Re-evaluation of cell types that exhibit the ability to die during spermatogenesis. Cell Prolif. 29:13-31.
6. Bozec, A., Chuzel, F., Chater, S., Paulin, C., Bars, R., Benahmed, M., and Mauduit, C. (2004). The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens. J. Endocrinol 183:79-90.
7. Brinkworth, M.H., Weinbauer, G.F., Schlatt, S., and Nieschlag, E. (1995). Identification of male germ cells undergoing apoptosis in adult rats. J. Reprod. Fertil. 105:25-33.
8. Burr, K.L., Smith, A.G., and Dubrova, Y.E. (2005). p53 deficiency does not affect mutation rate in the mouse germline. Oncogene 24:4315-4318.
9. Cai, L., Hales, B.F., and Robaire, B. (1997). Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol. Reprod. 56:1490-1497.
10. Cai, L., Jiang, J., Wang, B., Yao, H., and Wang, X. (1993). Induction of an adaptive response to dominant lethality and to chromosome damage of mouse germ cells by low dose radiation. Mutat. Res. 303:157-161.
11. Cai, L., and Liu, S.Z. (1990). Induction of cytogenetic adaptive response of somatic and germ cells in vivo and in vitro by low-dose X-irradiation. Int. J. Radiat. Biol. 58:187-194.
12. Cai, L., and Wang, P. (1995). Induction of a cytogenetic adaptive response in germ cells of irradiated mice with very low-dose rate of chronic gamma-irradiation and its biological influence on radiation-induced DNA or chromosomal damage and cell killing in their male offspring. Mutagenesis 10:95-100.
13. Cai, L., Wang, P., and Piao, X.G. (1994). Cytogenetic adaptive response with multiple small x-ray doses in mouse germ cells and its biological influence on the offspring of adapted males. Mutat. Res. 324:13-17.
14. Calabrese, E.J., Bachmann, K.A., Bailer, A.J., Bolger, P.M., Borak, J., Cai, L., Cedergreen, N., Cherian, M.G., Chiueh, C.C., Clarkson, T.W., et al. (2007). Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol. Appl. Pharmacol. 7:Epub ahead of print.
15. Calabrese, E.J., and Baldwin, L.A. (2000). Radiation hormesis: Its historical foundations as a biological hypothesis. Hum. Exp. Toxicol. 19:41-75.
16. Calabrese, E.J., and Baldwin, L.A. (2002). Defining hormesis. Hum. Exp. Toxicol. 21:91-97.
17. Castanares, M., Vera, Y., Erkkila, K., Kyttanen, S., Lue, Y., Dunkel, L., Wang, C., Swerdloff, R.S., and Hikim, A.P. (2005). Minocycline up-regulates BCL-2 levels in mitochondria and attenuates male germ cell apoptosis. Biochem. Biophys. Res. Commun. 337:663-669.
18. Chandrasekaran, Y., and Richburg, J.H. (2005). The p53 protein influences the sensitivity of testicular germ cells to mono-(2-ethylhexyl) phthalate-induced apoptosis by increasing the membrane levels of Fas and DR5 and decreasing the intracellular amount of c-FLIP. Biol. Reprod. 72: 206-213.
19. Chen, S.L., Cai, L., Meng, Q.Y., Xu, S., Wan, H., and Liu, S.Z. (2000). Low-dose whole-body irradiation (LD-WBI) changes protein expression of mouse thymocytes: Effect of a LD-WBI-enhanced protein RIP10 on cell proliferation and spontaneous or radiation-induced thymocyte apoptosis. Toxicol. Sci. 55:97-106.
20. Chen, Z., and Sakai, K. (2004). Enhancement of radiation-induced apoptosis by preirradiation with low-dose x-rays in human leukemia MOLT-4 cells. J. Radiat. Res. (Tokyo) 45:239-243.
21. Cisternas, P., and Moreno, R.D. (2006). Comparative analysis of apoptotic pathways in rat, mouse, and hamster spermatozoa. Mol. Reprod. Dev. 73:1318-1325.
22. Clarke, A.R., Purdie, C.A., Harrison, D.J., Morris, R.G., Bird, C.C., Hooper, M.L., and Wyllie, A.H. (1993). Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362:849-852.
23. Coleman, M.A., Yin, E., Peterson, L.E., Nelson, D., Sorensen, K., Tucker, J.D., and Wyrobek, A.J. (2005). Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response. Radiat. Res. 164:369-382.
24. Cordelli, E., Fresegna, A.M., Leter, G., Eleuteri, P., Spano, M., and Villani, P. (2003). Evaluation of DNA damage in different stages of mouse spermatogenesis after testicular X irradiation. Radiat. Res. 160: 443-451.
25. Cregan, S.P., Brown, D.L., and Mitchel, R.E. (1999). Apoptosis and the adaptive response in human lymphocytes. Int. J. Radiat. Biol. 75:1087-1094.
26. Deng, D.X., Cai, L., Chakrabarti, S., and Cherian, M.G. (1999). Increased radiation-induced apoptosis in mouse thymus in the absence of metallothionein. Toxicology 134:39-49.
27. Ding, L.H., Shingyoji, M., Chen, F., Hwang, J.J., Burma, S., Lee, C., Cheng, J.F., and Chen, D.J. (2005). Gene expression profiles of normal human fibroblasts after exposure to ionizing radiation: a comparative study of low and high doses. Radiat. Res. 164:17-26.
28. Embree-Ku, M., Venturini, D., and Boekelheide, K. (2002). Fas is involved in the p53-dependent apoptotic response to ionizing radiation in mouse testis. Biol. Reprod. 66:1456-1461.
29. Enns, L., Bogen, K.T., Wizniak, J., Murtha, A.D., and Weinfeld, M. (2004). Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis. Mol. Cancer Res. 2:557-566.
30. Franco, N., Lamartine, J., Frouin, V., Le Minter, P., Petat, C., Leplat, J.J., Libert, F., Gidrol, X., and Martin, M.T. (2005). Low-dose exposure to gamma rays induces specific gene regulations in normal human keratinocytes. Radiat. Res. 163:623-635.
31. Ghiassi-nejad, M.S., and Cameton J.R. (2002). Very high background radiation areas of Ramsar, Iran: Prelimary biological studies. Health Phys. 82:87-93.
32. Gong, S.L., Liu, S.C., Liu, J.X., Zhang, Y.C., and Liu, S.Z. (2000). Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose x-ray irradiation in mice. Biomed. Environ. Sci. 13:180-188.
33. Haines, G.A., Hendry, J.H., Daniel, C.P., and Morris, I.D. (2002). Germ cell and dose-dependent DNA damage measured by the comet assay in murine spermatozoaa after testicular X-irradiation. Biol. Reprod. 67:854-861.
34. Hamer, G., Gademan, I.S., Kal, H.B., and de Rooij, D.G. (2001). Role for c-Abl and p73 in the radiation response of male germ cells. Oncogene 20:4298-4304.
35. Hamer, G., Roepers-Gajadien, H.L., Gademan, I.S., Kal, H.B., and De Rooij, D.G. (2003). Intercellular bridges and apoptosis in clones of male germ cells. Int. J. Androl 26:348-353.
36. Hasegawa, M., Wilson, G., Russell, L.D., and Meistrich, M.L. (1997). Radiation-induced cell death in the mouse testis: relationship to apoptosis. Radiat. Res. 147:457-467.
37. Hasegawa, M., Zhang, Y., Niibe, H., Terry, N.H., and Meistrich, M.L. (1998). Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat. Res. 149:263-270.
38. Henriksen, K., Hakovirta, H., and Parvinen, M. (1995). In-situ quantification of stage-specific apoptosis in the rat seminiferous epithelium: Effects of short-term experimental cryptorchidism. Int. J. Androl. 18:256-262.
39. Heyer, B.S., MacAuley, A., Behrendtsen, O., and Werb, Z. (2000). Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development. Genes Dev. 14:2072-2084.
40. Hirota, A., Kawachi, Y., Itoh, K., Nakamura, Y., Xu, X., Banno, T., Takahashi, T., Yamamoto, M., and Otsuka, F. (2005). Ultraviolet A irradiation induces NF-E2-related factor 2 activation in dermal fibroblasts: Protective role in UVA-induced apoptosis. J. Invest. Dermatol. 124:825-832.
41. Hirst, C.E., Buzza, M.S., Sutton, V.R., Trapani, J.A., Loveland, K.L., and Bird, P.I. (2001). Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction. Mol. Hum. Reprod. 7:1133-1142.
42. Hussein, M.R., Abu-Dief, E.E., Abou El-Ghait, A.T., Adly, M.A., and Abdelraheem, M.H. (2006). Morphological evaluation of the radioprotective effects of melatonin against x-ray-induced early and acute testis damage in Albino rats: an animal model. Int. J. Exp. Pathol. 87:237-250.
43. Ishii, K., and Watanabe, M. (1996). Participation of gap-junctional cell communication on the adaptive response in human cells induced by low dose of x-rays. Int. J. Radiat. Biol. 69:291-299.
44. Joksic, G., and Petrovic, S. (2004). Lack of adaptive response of human lymphocytes exposed in vivo to low doses of ionizing radiation. J. Environ. Pathol. Toxicol. Oncol. 23:195-206.
45. Kang, K.W., Choi, S.H., and Kim, S.G. (2002). Peroxynitrite activates NF-E2-related factor 2/antioxidant response element through the pathway of phosphatidylinositol 3-kinase: The role of nitric oxide synthase in rat glutathione S-transferase A2 induction. Nitric Oxide 7:244-253.
46. Kang, K.W., Lee, S.J., and Kim, S.G. (2005). Molecular mechanism of nrf2 activation by oxidative stress. Antioxidant Redox. Signal. 7:1664-1673.
47. Kensler, T.W., Wakabayashi, N., and Biswal, S. (2007). Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 47:89-116.
48. Kim, Y.M., Yang, I., Lee, J., and Koo, H.S. (2005). Deficiency of Bloom's syndrome protein causes hypersensitivity of C. elegans to ionizing radiation but not to UV radiation, and induces p53-dependent physiological apoptosis. Mol. Cells 20:228-234.
49. Koana, T., Okada, M.O., Ogura, K., Tsujimura, H., and Sakai, K. (2007). Reduction of background mutations by low-dose X irradiation of Drosophila spermatocytes at a low dose rate. Radiat. Res. 167:217-221.
50. Koji, T., and Hishikawa, Y. (2003). Germ cell apoptosis and its molecular trigger in mouse testes. Arch. Histol. Cytol. 66:1-16.
51. Korystov, Y.N., Eliseeva, N.A., Kublik, L.N., and Narimanov, A.A. (1996). The effect of low-dose irradiation on proliferation of mammalian cells in vitro. Radiat. Res. 146:329-332.
52. Kumamoto, H., Ohki, K., and Ooya, K. (2005). Expression of p63 and p73 in ameloblastomas. J. Oral. Pathol. Med. 34:220-226.
53. Kunugita, N., Kakihara, H., Kawamoto, T., and Norimura, T. (2002). Micronuclei induced by low dose rate irradiation in early spermatids of p53 null and wild mice. J. Radiat. Res. 43:S205-207.
54. Lambrot, R., Coffigny, H., Pairault, C., Lecureuil, C., Frydman, R., Habert, R., and Rouiller-Fabre, V. (2007). High radiosensitivity of germ cells in human male fetus. J. Clin. Endocrinol. Metab. 24:Epub ahead of print.
55. Leblond, C.P., and Clermont, Y. (1952). Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann. NY Acad. Sci. 55:548-573.
56. Lee, J., Richburg, J.H., Shipp, E.B., Meistrich, M.L., and Boekelheide, K. (1999). The Fas system, a regulator of testicular germ cell apoptosis, is differentially up-regulated in Sertoli cell versus germ cell injury of the testis. Endocrinology 140:852-858.
57. Lee, N.P., Leung, K.W., Wo, J.Y., Tam, P.C., Yeung, W.S., and Luk, J.M. (2006). Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis 11:1215-1229.
58. Liu, G., Gong, P., Zhao, H., Wang, Z., Gong, S., and Cai, L. (2006). Effect of low-level radiation on the death of male germ cells. Radiat. Res. 165:379-389.
59. Liu, S.Z., Zhang, Y.C., Mu, Y., Su, X., and Liu, J.X. (1996). Thymocyte apoptosis in response to low-dose radiation. Mutat. Res. 358:185-191.
60. Luckey, T.D. (1982). Physiological benefits from low levels of ionizing radiation. Health Phys. 43:771-789.
61. Mohammadi, S.T.-D.M., Gharaati, M.R., Masoomi, R., and Ghiassi-Nejad, M. (2006). Adaptive response of blood lymphocytes of inhabitants residing in high background radiation areas of Ramsar - Micronuclei, apoptosi s and comet assays. J. Radiat. Res. (Tokyo) 21:135-140.
62. Morales, E., Ferrer, C., Zuasti, A., Garcia-Borron, J.C., Canteras, M., and Pastor, L.M. (2007). Apoptosis and molecular pathways in the seminiferous epithelium of aged and photoinhibited syrian hamsters (Mesocricetus auratus). J. Androl. 28:123-135.
63. Moreno, S.G., Dutrillaux, B., and Coffigny, H. (2001). High sensitivity of rat foetal germ cells to low dose-rate irradiation. Int. J. Radiat. Biol. 77:529-538.
64. Nagasawa, H., and Little, J.B. (1999). Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: Evidence for a bystander effect. Radiat. Res. 152:552-557.
65. Nair, R., and Shaha, C. (2003). Diethylstilbestrol induces rat spermatogenic cell apoptosis in vivo through increased expression of spermatogenic cell Fas/FasL system. J. Biol. Chem. 278:6470-6481.
66. National Research Council of the National Academies. (2006). Health risks from exposure to low levels of ionizing radiation: BEIR VII Phase 2. The National Academies Press, Washington, DC.
67. Olivieri, G., Bodycote, J., and Wolff, S. (1984). Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 223:594-597.
68. Ono, T., Ikehata, H., Vishnu Priya, P., and Uehara, Y. (2003). Molecular nature of mutations induced by irradiation with repeated low doses of x-rays in spleen, liver, brain and testis of lacZ-transgenic mice. Int. J. Radiat. Biol. 79:635-641.
69. Osburn, W.O., Wakabayashi, N., Misra, V., Nilles, T., Biswal, S., Trush, M.A., and Kensler, T.W. (2006). Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Arch. Biochem. Biophys. 454:7-15.
70. Otala, M., Suomalainen, L., Pentikainen, M.O., Kovanen, P., Tenhunen, M., Erkkila, K., Toppari, J., and Dunkel, L. (2004). Protection from radiation-induced male germ cell loss by sphingosine-1-phosphate. Biol. Reprod. 70:759-767.
71. Otsuka, K., Koana, T., Tauchi, H., and Sakai, K. (2006). Activation of antioxidative enzymes induced by low-dose-rate whole-body gamma irradiation: Adaptive response in terms of initial DNA damage. Radiat. Res. 166:474-478.
72. Park, S.H., Lee, Y., Jeong, K., Yoo, S.Y., Cho, C.K., and Lee, Y.S. (1999). Different induction of adaptive response to ionizing radiation in normal and neoplastic cells. Cell. Biol. Toxicol. 15:111-119.
73. Peltola, V., Parvinen, M., Huhtaniemi, I., Kulmala, J., and Ahotupa, M. (1993). Comparison of effects of 0.5 and 3.0 Gy X-irradiation on lipid peroxidation and antioxidant enzyme function in rat testis and liver. J. Androl. 14:267-274.
74. Petre-Lazar, B., Livera, G., Moreno, S.G., Trautmann, E., Duquenne, C., Hanoux, V., Habert, R., and Coffigny, H. (2007). The role of p63 in germ cell apoptosis in the developing testis. J. Cell. Physiol. 210:87-98.
75. Pinon-Lataillade, G., Velez de la Calle, J.F., Viguier-Martinez, M.C., Garnier, D.H., Folliot, R., Maas, J., and Jegou, B. (1988). Influence of germ cells upon Sertoli cells during continuous low-dose rate gamma-irradiation of adult rats. Mol. Cell. Endocrinol. 58:51-63.
76. Planel, H., Soleilhavoup, J.P., Tixador, R., Richoilley, G., Conter, A., Croute, F., Caratero, C., and Gaubin, Y. (1987). Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. Health Phys. 52:571-578.
77. Rasoulpour, T., DiPalma, K., Kolvek, B., and Hixon, M. (2006). Akt1 suppresses radiation-induced germ cell apoptosis in vivo. Endocrinology 147:4213-4221.
78. Richburg, J.H. (2000). The relevance of spontaneous- and chemically-induced alterations in testicular germ cell apoptosis to toxicology. Toxicol. Lett. 113:79-86.
79. Rodriguez, I., Ody, C., Araki, K., Garcia, I., and Vassalli, P. (1997). An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. EMBO J. 16:2262-2270.
80. Rotter, V., Schwartz, D., Almon, E., Goldfinger, N., Kapon, A., Meshorer, A., Donehower, L.A., and Levine, A.J. (1993). Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome. Proc. Natl. Acad. Sci. USA 90:9075-9079.
81. Russell, L.D., Ettlin, R.A., Sinha Hikim, A.P., and Clegg, E.D. 1990. Histological and histopathological evaluation of the testis. Philadelphia, PA: Cache River Press.
82. Sasagawa, I., Yazawa, H., Suzuki, Y., and Nakada, T. (2001). Stress and testicular germ cell apoptosis. Arch. Androl. 47:211-216.
83. Schwartz, D., Goldfinger, N., and Rotter, V. (1993). Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene 8:1487-1494.
84. Scott, B.R. (2004). A biological-based model that links genomic instability, bystander effects, and adaptive response. Mutati. Res. 568:129-143.
85. Seong, J., Kim, S.H., Pyo, H.R., Chung, E.J., and Suh, C.O. (2001). Effect of low-dose irradiation on induction of an apoptotic adaptive response in the murine system. Radiat. Environ. Biophys. 40:335-339.
86. Shaposhnikova, V.V., and Korystov, Y.N. (1995). Thymocyte proliferation and apoptosis induced by ionizing radiation. Scan. Microsc. 9:1203-1206.
87. Sinha Hikim, A.P., Lue, Y., Diaz-Romero, M., Yen, P.H., Wang, C., and Swerdloff, R.S. (2003). Deciphering the pathways of germ cell apoptosis in the testis. J. Steroid. Biochem. Mol. Biol. 85:175-182.
88. Somers, C.M., Sharma, R., Quinn, J.S., and Boreham, D.R. (2004). Gamma radiation-induced heritable mutations at repetitive DNA loci in out-bred mice. Mutat. Res. 568:69-78.
89. Spierings, D.C., de Vries, E.G., Stel, A.J., te Rietstap, N., Vellenga, E., and de Jong, S. (2004). Low p21Waf1/Cip1 protein level sensitizes testicular germ cell tumor cells to Fas-mediated apoptosis. Oncogene 23:4862-4872.
90. Stambolsky, P., Weisz, L., Shats, I., Klein, Y., Goldfinger, N., Oren, M., and Rotter, V. 2006. Regulation of AIF expression by p53. Cell. Death Differ. 13:2140-2149.
91. Suzuki, K., Kodama, S., and Watanabe, M. (2001). Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res. 61:5396-5401.
92. Takano, N., Matusi, H., and Takahashi, T. (2004). Granzyme N, a novel granzyme, is expressed in spermatocytes and spermatids of the mouse testis. Biol. Reprod. 71:1785-1795.
93. Taylor, S.L., W.S., Fox, P., Duran, E.H., Morshedi, M.S., Oehninger, S., and Beebe, S.J. (2004). Somatic cell apoptosis markers and pathways in human ejaculated sperm: Potential utility as indicators of sperm quality. Mol. Hum. Reprod. 10:825-834.
94. UNSCEAR Report Aunex B. (1994). Adaptive responses to radiation in cells and organisms. United Nations, New York, 302-338.
95. Vera, Y., Erkkila, K., Wang, C., Nunez, C., Kyttanen, S., Lue, Y., Dunkel, L., Swerdloff, R.S., and Sinha Hikim, A.P. (2006). Involvement of p38 mitogen-activated protein kinase and inducible nitric oxide synthase in apoptotic signaling of murine and human male germ cells after hormone deprivation. Mol. Endocrinol. 20:1597-1609.
96. Verheij, M., and Bartelink, H. (2000). Radiation-induced apoptosis. Cell. Tissue. Res. 301:133-142.
97. Vydra, N., Malusecka, E., Jarzab, M., Lisowska, K., Glowala-Kosinska, M., Benedyk, K., Widlak, P., Krawczyk, Z., and Widlak, W. (2006). Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells. Cell. Death. Differ. 13:212-222.
98. Wang, G.J., and Cai, L. (2000). Induction of cell-proliferation hormesis and cell-survival adaptive response in mouse hematopoietic cells by whole-body low-dose radiation. Toxicol. Sci. 53:369-376.
99. Wang, X., Matsumoto, H., Okaichi, K., and Ohnishi, T. (1996). p53 accumulation in various organs of rats after whole-body exposure to low-dose x-ray irradiation. Anticancer Res. 16:1671-1674.
100. Xu, X., Aprelikova, O., Moens, P., Deng, C.X., and Furth, P.A. (2003). Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development 130:2001-2012.
101. Zhang, H., Liu, B., Zhou, Q., Zhou, G., Yuan, Z., Li, W., Duan, X., Min, F., Xie, Y., and Li, X. (2006). Alleviation of preexposure of mouse brain with low-dose C ion or Co gamma-ray on male reproductive endocrine damages induced by subsequent high-dose irradiation. Int. J. Androl. 29:592-596.
102. Zhang, H., Zheng, R.L., Wei, Z.Q., Li, W.J., Gao, Q.X., Chen, W.Q., Wang, Z.H., He, J., Liang, J.P., Han, G.W., et al. (1998). Effects of preexposure of mouse testis with low-dose (16)O8+ ions or 60Co gamma-rays on sperm shape abnormalities, lipid peroxidation and superoxide dismutase (SOD) activity induced by subsequent high-dose irradiation. Int. J. Radiat. Biol. 73:163-167.