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Hum. Reprod. Advance Access published online on August 24, 2006

Human Reproduction, doi:10.1093/humrep/del292
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received March 9, 2006
Revised June 21, 2006
Accepted June 27, 2006

Article

Sperm DNA integrity in testicular cancer patients

O. Ståhl 1 *, J. Eberhard 1, K. Jepson 2, M. Spano 3, M. Cwikiel 4, E. Cavallin-Ståhl 4, and A. Giwercman 2

1 Department of Oncology, Lund University Hospital, Lund, Sweden; Fertility Centre and Department of Urology, Scanian Andrology Centre, Malmö University Hospital, Malmö, Sweden
2 Fertility Centre and Department of Urology, Scanian Andrology Centre, Malmö University Hospital, Malmö, Sweden
3 Section of Toxicology and Biomedical Sciences, BIOTEC-MED, ENEA Casaccia Research Center, Rome, Italy
4 Department of Oncology, Lund University Hospital, Lund, Sweden

* To whom correspondence should be addressed.
O. Ståhl, E-mail: olof.stahl{at}med.lu.se


   Abstract

BACKGROUND: We evaluated the impact of testicular germ cell cancer (TGCC), its treatment and length of follow-up on sperm DNA integrity. METHODS: In 96 TGCC patients, semen was collected at specific intervals until 5 years after treatment. Sperm DNA integrity was assessed by the sperm chromatin structure assay (SCSA, n = 193) and by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL, n = 159) assay. Results were expressed as DNA fragmentation index (DFI). Controls comprised of 278 military conscripts. RESULTS: Post-surgery testicular cancer (TC) patients did not differ from controls. Compared with pretreatment values, radiotherapy induced a transient increase in SCSADFI (medians: 12 versus 19%; P = 0.03), normalizing after 3-5 years. One year or more after therapy, 5/13 (38%) of normozoospermic, irradiated patients had SCSADFI >27% compared with 7% of normozoospermic controls (P = 0.002). More than two cycles of chemotherapy decreased DFI 3-5 years post-therapy (median SCSADFI: 12 versus 9.1%, P = 0.02; median TUNELDFI: 11 versus 7.5%, P = 0.03). CONCLUSION: Irradiation increases sperm DNA damage 1-2 years after treatment, and 38% of irradiated patients with normozoospermia had high (>27%) DNA damage, which may affect the sperm-fertilizing ability. TC per se is not associated with an increase of DFI, and DFI is reduced by three or more cycles of chemotherapy.

Keywords: chemotherapy/radiotherapy/SCSA/sperm DNA/testicular cancer/TUNEL.
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