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Published-Ahead-of-Print October 4, 2006, DOI:10.2164/jandrol.106.001487
Journal of Andrology, Vol. 28, No. 2, March/April 2007
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.106.001487

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Effects of the Chemotherapy Cocktail Used to Treat Testicular Cancer on Sperm Chromatin Integrity

GÉRALDINE DELBES*, BARBARA F. HALES* AND BERNARD ROBAIRE*,{dagger}

From the Departments of * Pharmacology and Therapeutics and of {dagger} Obstetrics and Gynecology, McGill University, Montréal, Québec, Canada.

Correspondence to: Bernard Robaire, Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William Osler, Montréal, Québec, Canada H3G 1Y6 (e-mail: bernard.robaire{at}mcgill.ca).


The incidence of testicular cancer has increased dramatically over the past 50 years. Advances in treatment, which include the coadministration of bleomycin, etoposide, and cis-platinum (BEP), have brought the cure rate to over 90%. After treatment, most patients go through a temporary period of azoo/oligozoospermia. Although the sperm concentration in approximately 80% of the patients returns to at least 10 million/mL, little is known about the integrity of the chromatin of their germ cells. Using an animal model, we assessed DNA integrity in the spermatozoa of male rats treated for 3, 6 or 9 weeks with BEP at doses, adjusted for surface area, equivalent to 0X, 1/3X, 2/3X, or 1X of the human dose. We did not observe any difference in protamination content, as assessed by the chromomycin A3 (CMA3) assay. After 9 weeks of 1X treatment, the susceptibility of DNA to denaturation evaluated by the sperm chromatin structure assay (SCSA®)/acridine orange assay (AO) was increased, as well as the number of single and double DNA strand breaks measured by the TUNEL and COMET assays. Parameters obtained from the AO and TUNEL assays were highly correlated with the motility of the spermatozoa, suggesting that conventional sperm analysis parameters can serve as a good indicator of chromatin integrity and vice versa. Correlation studies also suggested that the parameters obtained with the different assays do not overlap, but complement each other. Thus, BEP treatment altered spermatozoal chromatin quality, and these alterations may impact adversely on progeny outcome.

     Key words: Sperm DNA, DNA strand breaks




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F. Vaisheva, G. Delbes, B. F. Hales, and B. Robaire
Effects of the Chemotherapeutic Agents for Non-Hodgkin Lymphoma, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), on the Male Rat Reproductive System and Progeny Outcome
J Androl, July 1, 2007; 28(4): 578 - 587.
[Abstract] [Full Text] [PDF]


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