Effects of acute and chronic cyclophosphamide treatment on meiotic progression and the induction of DNA double-strand breaks in rat spermatocytes

Biology of Reproduction

Volumn 72, Issue 6, 2005, Pages 1297-1304

  Aguilar Mahecha, Adriana ^a   Hales, Barbara F ^a   Robaire, Bernard ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Meiosis; Spermatogenesis; Stress; Toxicology

Indexed keywords

ALKYLATING AGENT; CYCLOPHOSPHAMIDE; OKADAIC ACID;

ACUTE DRUG ADMINISTRATION; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL CULTURE; CELL CYCLE; CELL CYCLE PHASE; CHRONIC DRUG ADMINISTRATION; DEFENSE MECHANISM; DNA DAMAGE; DNA STRAND BREAKAGE; DOSE RESPONSE; DRUG EFFECT; FLUORESCENCE; GENOTOXICITY; GERM CELL; IMMUNOCYTOCHEMISTRY; MALE; MEIOSIS; NONHUMAN; PACHYTENE; PRIORITY JOURNAL; PROGENY; RAT; SPERMATOCYTE; SPERMATOGENESIS; STATISTICAL ANALYSIS;

ANIMALS; CELLS, CULTURED; CYCLOPHOSPHAMIDE; DNA; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, DRUG; HISTONES; MALE; MEIOSIS; MUTAGENS; PHOSPHORYLATION; RATS; RATS, SPRAGUE-DAWLEY; SPERMATOCYTES;

EID: 18844377182     PISSN: 00063363     EISSN: None     Source Type: Journal    
DOI: 10.1095/biolreprod.104.038620     Document Type: Article

References (65)

1. Colvin OM. An overview of cyclophosphamide development and clinical applications. Curr Pharm Des 1999; 5:555-560.
2. Kenney LB, Laufer MR, Grant FD, Grier H, Diller L. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 2001; 91:613-621.
3. Charak BS, Gupta R, Mandrekar P, Sheth NA, Banavali SD, Saikia TK, Gopal R, Dinshaw KA, Advani SH. Testicular dysfunction after cyclophosphamide- vincristine-procarbazine-prednisolone chemotherapy for advanced Hodgkin's disease. A long-term follow-up study. Cancer 1990; 65:1903-1906.
4. Trasler JM, Hales BF, Robaire B. Chronic low-dose cyclophosphamide treatment of adult male-rats - effect on fertility, pregnancy outcome and progeny. Biol Reprod 1986; 34:275-283.
5. Trasler JM, Hales BF, Robaire B. A time-course study of chronic paternal cyclophosphamide treatment in rats - effects on pregnancy outcome and the male reproductive and hematologic systems. Biol Reprod 1987; 37:317-326.
6. Barton TS, Wyrobek AJ, Hill FS, Robaire B, Hales BF. Numerical chromosomal abnormalities in rat epididymal spermatozoa following chronic cyclophosphamide exposure. Biol Reprod 2003; 69:1150-1157.
7. Sotomayor RE, Cumming RB. Induction of translocations by cyclophosphamide in different germ-cell stages of male mice - cytological characterization and transmission. Mutat Res 1975; 27:375-388.
8. Tates AD. Validation studies with the micronucleus test for early spermatids of rats. A tool for detecting clastogenicity of chemicals in differentiating spermatogonia and spermatocytes. Mutagenesis 1992; 7:411-419.
9. Lahdetie J. Micronuclei induced during meiosis by ethyl methanesulfonate, cyclophosphamide and dimethylbenzanthracene in male rats. Mutat Res 1983; 120:257-260.
10. Lahdetie J. Induction and survival of micronuclei in rat spermatids. Comparison of two meiotic micronucleus techniques using cyclophosphamide. Mutat Res 1988; 203:47-53.
11. Schimenti KJ, Hanneman WH, Schimenti JC. Evidence for cyclophosphamide-induced gene conversion and mutation in mouse germ cells. Toxicol Appl Pharmacol 1997; 147:343-350.
12. Backer LC, Gibson JB, Moses MJ, Allen JW. Synaptonemal complex damage in relation to meiotic chromosome aberrations after exposure of male mice to cyclophosphamide. Mutat Res 1988; 203:317-330.
13. Allen JW, DeWeese GK, Gibson JB, Poorman PA, Moses MJ. Synaptonemal complex damage as a measure of chemical mutagen effects on mammalian germ cells. Mutat Res 1987; 190:19-24.
14. Allen JW, Gibson JB, Poorman PA, Backer LC, Moses MJ. Synaptonemal complex damage induced by clastogenic and anti-mitotic chemicals: implications for non-disjunction and aneuploidy. Mutat Res 1988; 201:313-324.
15. Aguilar-Mahecha A, Hales BF, Robaire B. Expression of stress response genes in germ cells during spermatogenesis. Biol Reprod 2001; 65:119-127.
16. Aguilar-Mahecha A, Hales BF, Robaire B. Acute cyclophosphamide exposure has germ cell specific effects on the expression of stress response genes during rat spermatogenesis. Mol Reprod Dev 2001; 60:302-311.
17. Aguilar-Mahecha A, Hales BF, Robaire B. Chronic cyclophosphamide treatment alters the expression of stress response genes in rat male germ cells. Biol Reprod 2002; 66:1024-1032.
18. Codrington AM, Hales BF, Robaire B. Spermiogenic germ cell phase-specific DNA damage following cyclophosphamide exposure. J Androl 2004; 25:354-362.
19. Qiu J, Hales BF, Robaire B. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure. Biol Reprod 1995; 53:1465-1473.
20. Robaire B, Hales BF. Mechanisms of action of cyclophosphamide as a male-mediated developmental toxicant. Adv Exp Med Biol 2003; 518:169-180.
21. Cobb J, Handel MA. Dynamics of meiotic prophase I during spermatogenesis: from pairing to division. Semin Cell Dev Biol 1998; 9:445-450.
22. Handel MA. Monitoring meiosis in gametogenesis. Theriogenology 1998; 49:423-430.
23. Handel MA, Cobb J, Eaker S. What are the spermatocyte's requirements for successful meiotic division? J Exp Zool 1999; 285:243-250.
24. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 2004; 73:39-85.
25. Smits VA, Medema RH. Checking out the G(2)/M transition. Biochim Biophys Acta 2001; 1519:1-12.
26. Odorisio T, Rodriguez TA, Evans EP, Clarke AR, Burgoyne PS. The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nat Genet 1998; 18:257-261.
27. Sharan SK, Pyle A, Coppola V, Babus J, Swaminathan S, Benedict J, Swing D, Martin BK, Tessarollo L, Evans JP, Flaws JA, Handel MA. BRCA2 deficiency in mice leads to meiotic impairment and infertility. Development 2004; 131:131-142.
28. Edelmann W, Cohen PE, Kneitz B, Winand N, Lia M, Heyer J, Kolodner R, Pollard JW, Kucherlapati R. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet 1999; 21:123-127.
29. Kneitz B, Cohen PE, Avdievich E, Zhu L, Kane MF, Hou H Jr, Kolodner RD, Kucherlapati R, Pollard JW, Edelmann W. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev 2000; 14:1085-1097.
30. Pittman DL, Cobb J, Schimenti KJ, Wilson LA, Cooper DM, Brignull E, Handel MA, Schimenti JC. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol Cell 1998; 1:697-705.
31. Barlow C, Liyanage M, Moens PB, Tarsounas M, Nagashima K, Brown K, Rottinghaus S, Jackson SP, Tagle D, Ried T, Wynshaw-Boris A. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I. Development 1998; 125:4007-4017.
32. Eaker S, Cobb J, Pyle A, Handel MA. Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: insights into regulation of spermatogenic progress. Dev Biol 2002; 249:85-95.
33. Xu X, Aprelikova O, Moens P, Deng CX, Furth PA. Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development 2003; 130:2001-2012.
34. West A, Lahdetie J. X-irradiation-induced changes in the progression of type B spermatogonia and preleptotene spermatocytes. Mol Reprod Dev 2001; 58:78-87.
35. Schmid TE, Attia S, Baumgartner A, Nuesse M, Adler ID. Effect of chemicals on the duration of male meiosis in mice detected with laser scanning cytometry. Mutagenesis 2001; 16:339-343.
36. Rosiepen G, Chapin RE, Weinbauer GF. The duration of the cycle of the seminiferous epithelium is altered by administration of 2,5-hexanedione in the adult Sprague-Dawley rat. J Androl 1995; 16:127-135.
37. Schwartz D, Goldfinger N, Kam Z, Rotter V. p53 controls low DNA damage-dependent premeiotic checkpoint and facilitates DNA repair during spermatogenesis. Cell Growth Differ 1999; 10:665-675.
38. Handel MA, Caldwell KA, Wiltshire T. Culture of pachytene spermatocytes for analysis of meiosis. Dev Genet 1995; 16:128-139.
39. Wiltshire T, Park C, Caldwell KA, Handel MA. Induced premature G2/M-phase transition in pachytene spermatocytes includes events unique to meiosis. Dev Biol 1995; 169:557-567.
40. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 1999; 146:905-916.
41. Rogakou ER Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998; 273:5858-5868.
42. Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A. H2AX: the histone guardian of the genome. DNA Repair (Amst) 2004; 3:959-967.
43. Bellvé AR, Millette CF, Bhatnagar YM, O'Brien DA. Dissociation of the mouse testis and characterization of isolated spermatogenic cells. J Histochem Cytochem 1977; 25:480-494.
44. Evans EP, Breckon G, Ford CE. An air-drying method for meiotic preparations from mammalian testes. Cytogenetics 1964; 15:289-294.
45. Tarsounas M, Pearlman RE, Moens PB. Meiotic activation of rat pachytene spermatocytes with okadaic acid: the behaviour of synaptonemal complex components SYN1/SCP1 and COR1/SCP3. J Cell Sci 1999; 112:423-434.
46. Peters AH, Plug AW, van Vugt MJ, de Boer P. A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res 1997; 5:66-68.
47. Sedelnikova OA, Rogakou EP, Panyutin IG, Bonner WM. Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma-H2AX antibody. Radiat Res 2002; 158:486-492.
48. Hamer G, Roepers-Gajadien HL, Duyn-Goedhart A, Gademan IS, Kal HB, van Buul PP, de Rooij DG. DNA double-strand breaks and gamma-H2AX signaling in the testis. Biol Reprod 2003; 68:628-634.
49. Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, Bonner WM, Manova K, Burgoyne P, Nussenzweig A. H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 2003; 4:497-508.
50. Nasonova E, Fussel K, Berger S, Gudowska-Nowak E, Ritter S. Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X-rays and 195 MeV u(-1) C ions. Int J Radiat Biol 2004; 80:621-634.
51. O'Connor PM, Ferris DK, Pagano M, Draetta G, Pines J, Hunter T, Longo DL, Kohn KW. G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem 1993; 268:8298-8308.
52. Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res 1995; 330:115-181.
53. Jachymczyk WJ, von Borstel RC, Mowat MR, Hastings PJ. Repair of interstrand cross-links in DNA of Saccharomyces cerevisiae requires two systems for DNA repair: the RAD3 system and the RAD51 system. Mol Gen Genet 1981; 182:196-205.
54. Niedernhofer LJ, Odijk H, Budzowska M, van Drunen E, Maas A, Theil AF, de Wit J, Jaspers NG, Beverloo HB, Hoeijmakers JH, Kanaar R. The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol 2004; 24:5776-5787.
55. Sjoblom T, West A, Lahdetie J. Apoptotic response of spermatogenic cells to the germ cell mutagens etoposide, adriamycin, and diepoxybutane. Environ Mol Mutagen 1998; 31:133-148.
56. Tepperberg JH, Moses MJ, Nath J. Colchicine effects on meiosis in the male mouse. I. Meiotic prophase: synaptic arrest, univalents, loss of damaged spermatocytes and a possible checkpoint at pachytene. Chromosoma 1997; 106:183-192.
57. Pacchierotti F, Bellincampi D, Civitareale D. Cytogenetic observations, in mouse secondary spermatocytes, on numerical and structural chromosome aberrations induced by cyclophosphamide in various stages of spermatogenesis. Mutat Res 1983; 119:177-183.
58. Cobb J, Reddy RK, Park C, Handel MA. Analysis of expression and function of topoisomerase I and II during meiosis in male mice. Mol Reprod Dev 1997; 46:489-498.
59. Cai L, Hales BF, Robaire B. Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod 1997; 56:1490-1497.
60. Sotomayor RE, Sega GA, Cumming RB. Unscheduled DNA synthesis in spermatogenic cells of mice treated in vivo with the indirect alkylating agents cyclophosphamide and mitomen. Mutat Res 1978; 50:229-240.
61. Nazarov IB, Smirnova AN, Krutilina RI, Svetlova MP, Solovjeva LV, Nikiforov AA, Oei SL, Zalenskaya IA, Yau PM, Bradbury EM, Tomilin NV. Dephosphorylation of histone gamma-H2AX during repair of DNA double-strand breaks in mammalian cells and its inhibition by calyculin A. Radiat Res 2003; 160:309-317.
62. Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 2000; 275:9390-9395.
63. Trasler JM, Hermo L, Robaire B. Morphological changes in the testis and epididymis of rats treated with cyclophosphamide: a quantitative approach. Biol Reprod 1988; 38:463-479.
64. Niwa O. Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies. Oncogene 2003; 22:7078-7086.
65. Xu X, Aprelikova O, Moens P, Deng CX, Furth PA. Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development 2003; 130:2001-2012.