PMID- 16311288 OWN - NLM STAT- MEDLINE DCOM- 20060605 LR - 20220331 IS - 0268-1161 (Print) IS - 0268-1161 (Linking) VI - 21 IP - 4 DP - 2006 Apr TI - Etoposide induces chromosomal abnormalities in mouse spermatocytes and stem cell spermatogonia. PG - 888-95 AB - BACKGROUND: Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukaemia, lymphomas and many solid tumours such as testicular and ovarian cancers, all of which are common in patients of reproductive age. The purpose of the study was to characterize the long-term effects of ET on male germ cells using sperm fluorescence in situ hybridization (FISH) analyses. METHODS: Chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies were detected in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. RESULTS: ET treatment resulted in major increases in the frequencies of sperm-carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. CONCLUSION: These results show that ET may have long-lasting effects on the frequencies of sperm with structural aberrations. This has important implications for cancer patients undergoing chemotherapy with ET because they may remain at higher risk for abnormal reproductive outcomes long after the end of chemotherapy. FAU - Marchetti, Francesco AU - Marchetti F AD - Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. marchetti2@llnl.gov FAU - Pearson, Francesca S AU - Pearson FS FAU - Bishop, Jack B AU - Bishop JB FAU - Wyrobek, Andrew J AU - Wyrobek AJ LA - eng GR - Y01-ES-8016-5/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20051125 PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 6PLQ3CP4P3 (Etoposide) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/*toxicity MH - Chromosome Aberrations/*chemically induced MH - Etoposide/*toxicity MH - In Situ Hybridization, Fluorescence MH - Male MH - Meiosis MH - Mice MH - Spermatocytes/*drug effects MH - Spermatogonia/*drug effects MH - Stem Cells/drug effects EDAT- 2005/11/29 09:00 MHDA- 2006/06/06 09:00 CRDT- 2005/11/29 09:00 PHST- 2005/11/29 09:00 [pubmed] PHST- 2006/06/06 09:00 [medline] PHST- 2005/11/29 09:00 [entrez] AID - dei416 [pii] AID - 10.1093/humrep/dei416 [doi] PST - ppublish SO - Hum Reprod. 2006 Apr;21(4):888-95. doi: 10.1093/humrep/dei416. Epub 2005 Nov 25.