Doxorubicin and vincristine affect undifferentiated rat spermatogonia - PubMed (original) (raw)
. 2017 Jun;153(6):725-735.
doi: 10.1530/REP-17-0005. Epub 2017 Mar 3.
Affiliations
- PMID: 28258155
- DOI: 10.1530/REP-17-0005
Doxorubicin and vincristine affect undifferentiated rat spermatogonia
Hermance Beaud et al. Reproduction. 2017 Jun.
Abstract
Anticancer drugs, such as alkylating agents, can affect male fertility by targeting the DNA of proliferative spermatogonial stem cells (SSC). Therefore, to reduce such side effects, other chemotherapeutics are used. However, less is known about their potential genotoxicity on SSC. Moreover, DNA repair mechanisms in SSC are poorly understood. To model treatments deprived of alkylating agents that are commonly used in cancer treatment, we tested the impact of exposure to doxorubicin and vincristine, alone or in combination (MIX), on a rat spermatogonial cell line with SSC characteristics (GC-6spg). Vincristine alone induced a cell cycle arrest and cell death without genotoxic impact. On the other hand, doxorubicin and the MIX induced a dose-dependent cell death. More importantly, doxorubicin and the MIX induced DNA breaks, measured by the COMET assay, at a non-cytotoxic dose. To elucidate which DNA repair pathway is activated in spermatogonia after exposure to doxorubicin, we screened the expression of 75 genes implicated in DNA repair. Interestingly, all were expressed constitutively in GC-6spg, suggesting great potential to respond to genotoxic stress. Doxorubicin treatments affected the expression of 16 genes (>1.5 fold change; P < 0.05) involved in cell cycle, base/nucleotide excision repair, homologous recombination and non-homologous end joining (NHEJ). The significant increase in CDKN1A and XRCC1 suggest a cell cycle arrest and implies an alternative NHEJ pathway in response to doxorubicin-induced DNA breaks. Together, our results support the idea that undifferentiated spermatogonia have the ability to respond to DNA injury from chemotherapeutic compounds and escape DNA break accumulation.
© 2017 Society for Reproduction and Fertility.
Similar articles
- In vitro study of doxorubicin-induced oxidative stress in spermatogonia and immature Sertoli cells.
Tremblay AR, Delbes G. Tremblay AR, et al. Toxicol Appl Pharmacol. 2018 Jun 1;348:32-42. doi: 10.1016/j.taap.2018.04.014. Epub 2018 Apr 13. Toxicol Appl Pharmacol. 2018. PMID: 29660436 - Ku70 and Rad51 vary in their importance for the repair of doxorubicin- versus etoposide-induced DNA damage.
Schonn I, Hennesen J, Dartsch DC. Schonn I, et al. Apoptosis. 2011 Apr;16(4):359-69. doi: 10.1007/s10495-010-0564-y. Apoptosis. 2011. PMID: 21107697 - Effects of four chemotherapeutic agents, bleomycin, etoposide, cisplatin, and cyclophosphamide, on DNA damage and telomeres in a mouse spermatogonial cell line.
Liu M, Hales BF, Robaire B. Liu M, et al. Biol Reprod. 2014 Apr 3;90(4):72. doi: 10.1095/biolreprod.114.117754. Print 2014 Apr. Biol Reprod. 2014. PMID: 24571982 - BMP4-induced differentiation of a rat spermatogonial stem cell line causes changes in its cell adhesion properties.
Carlomagno G, van Bragt MP, Korver CM, Repping S, de Rooij DG, van Pelt AM. Carlomagno G, et al. Biol Reprod. 2010 Nov;83(5):742-9. doi: 10.1095/biolreprod.110.085456. Epub 2010 Jul 21. Biol Reprod. 2010. PMID: 20650884 - Targeting cancer-specific synthetic lethality in double-strand DNA break repair.
Moeller BJ, Pasqualini R, Arap W. Moeller BJ, et al. Cell Cycle. 2009 Jun 15;8(12):1872-6. doi: 10.4161/cc.8.12.8743. Epub 2009 Jun 15. Cell Cycle. 2009. PMID: 19440052 Review.
Cited by
- Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm quality maintaining.
Zi T, Liu Y, Zhang Y, Wang Z, Wang Z, Zhan S, Peng Z, Li N, Liu X, Liu F. Zi T, et al. Reprod Biol Endocrinol. 2022 Jul 18;20(1):105. doi: 10.1186/s12958-022-00977-4. Reprod Biol Endocrinol. 2022. PMID: 35850689 Free PMC article. - Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility.
Delessard M, Saulnier J, Rives A, Dumont L, Rondanino C, Rives N. Delessard M, et al. Int J Mol Sci. 2020 Feb 20;21(4):1454. doi: 10.3390/ijms21041454. Int J Mol Sci. 2020. PMID: 32093393 Free PMC article. Review. - Sperm DNA integrity in adult survivors of paediatric leukemia and lymphoma: A pilot study on the impact of age and type of treatment.
Beaud H, Albert O, Robaire B, Rousseau MC, Chan PTK, Delbes G. Beaud H, et al. PLoS One. 2019 Dec 19;14(12):e0226262. doi: 10.1371/journal.pone.0226262. eCollection 2019. PLoS One. 2019. PMID: 31856166 Free PMC article. - Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats.
Ahmed ZA, Abtar AN, Othman HH, Aziz TA. Ahmed ZA, et al. Drug Des Devel Ther. 2019 Sep 20;13:3321-3329. doi: 10.2147/DDDT.S222127. eCollection 2019. Drug Des Devel Ther. 2019. PMID: 31571833 Free PMC article. - New insights into the activities and toxicities of the old anticancer drug doxorubicin.
van der Zanden SY, Qiao X, Neefjes J. van der Zanden SY, et al. FEBS J. 2021 Nov;288(21):6095-6111. doi: 10.1111/febs.15583. Epub 2020 Oct 19. FEBS J. 2021. PMID: 33022843 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous