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RECHERCHER

DNA repair in spermatogonia after exposure to doxorubicin alone or in mixture with vincristine

Beaud, Hermance; Van Pelt, AM; Delbès, Géraldine . DNA repair in spermatogonia after exposure to doxorubicin alone or in mixture with vincristine In: 9ème symposium annuel du Réseau Québécois en Reproduction, Novembre 2016, Québec.

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Résumé

Chemotherapy could affect male fertility by targeting the proliferative spermatogonial stem cells (SSC) in the prepubertal testis; all unrepaired DNA damage could spread through spermatogenesis cycles, and could in term affect sperm quality. Modelling treatments of most hematologic childhood cancer on SSC lineage (GC - 6spg), we support the hypothesis that exposure to non - cytotoxic doses of doxorubicin alone or in combination with vincristine (MIX) trigger a DNA damage response in SSC.

Our dose - dependent study, using the MTT and COMET assays, revealed the induction of DNA break after 24h exposure to non - cytotoxic dose of 0.1μM doxorubicin or MIX. Importantly, this significant increase of DNA breaks level recovered after two days compare to control. Interestingly, 75 DNA repair genes sc reened by PCR array were expressed constitutively in control GC - 6spg, suggesting that spermatogonia have all the resources available to respond to genotoxic impairment. Exposure to 0.1μM doxorubicin or MIX for 24h significantly dysregulated 14 and 13 genes respectively (≥1.5 fold change). Among these genes, 8 cell cycle or apoptosis genes and 7 genes involved in DNA repair were up - regulated. 50% of the DNA repair gene act in Base/Nucleotide Excision Repair (BER/NER) pathways. Semi - quantification by western blot revealed significant increase of CDKN1A and XRCC1, suggesting a cell cycle arrest and the importance of BER in spermatogonia in response to doxorubicin.

Understanding of the implication of this DNA repair pathways in SSC survival could open up new res earch avenues to prevent side effects of pediatric cancer treatment on male fertility.

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2018 15:43
Dernière modification: 01 mai 2018 15:43
URI: http://espace.inrs.ca/id/eprint/5940

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