Chemotherapy-induced cytotoxicity and genotoxicity to the bone marrow microenvironment

May, J E; Morse, H R; Page, K; Soh, M; Wexler, S; Cox, C; Xu, J; Donaldson, C

Abstract

The bone marrow (BM) microenvironment is largely com- prised of mesenchymal stromal cells (MSCs) and is vital in supporting haematopoiesis. Limited studies have indicated that the BM microenvironment is damaged by chemotherapy; however the extent and long-term effects of this are unknown. This may be particularly critical in stem cell transplant patients who receive high-dose chemotherapy prior to transplant, and whilst the incoming graft replaces haematopoietic cells, the microenvironment remains of host origin. Consequently, dam- age caused by chemotherapy may be permanent and possibly implicated in graft failure if haematopoietic support is com- promised. MSCs were isolated from BM samples from patients undergoing chemotherapy for haematological malignancies as well as untreated control BM obtained as a waste product dur- ing total hip replacements. Following chemotherapy, MSCs have reduced proliferative capacity and survival (p

• Journal Article Type: Article
• Acceptance Date: Jul 15, 2013
• Online Publication Date: Dec 18, 2013
• Publication Date: Jan 31, 2014
• Journal: Mutagenesis
• Print ISSN: 0267-8357
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 1
• Pages: 79
• DOI: https://doi.org/10.1093/mutage/get060
• Keywords: mutation, cancer, chemotherapy regimen, carcinogens, cell line, dna, dna damage, dna repair, genome, mammals, micronucleus, mutagens, pyrenes, bone marrow, mice, nanoparticles
• Public URL: https://uwe-repository.worktribe.com/output/821744
• Publisher URL: http://dx.doi.org/10.1093/mutage/get060