Browse by author
Lookup NU author(s): Dr Victoria Forster,
Dr Jill McKay
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 Dr Victoria J Forster. Methotrexate (MTX) is administered to treat childhood acute lymphoblastic leukemia (ALL). It acts by inhibiting dihydrofolate reductase which reduces methyltetrahydrofolate, a key component in one carbon metabolism, thus reducing cell proliferation. Further perturbations to one carbon metabolism, such as reduced Vitamin B12 levels via the use of nitrous oxide for sedation during childhood ALL treatment, may increase neurotoxicity risk. With B12 as an enzymatic cofactor, methyltetrahydrofolate is essential to produce methionine, which is critical for DNA methylation. We investigated global and gene specific DNA methylation in neuronal cell lines in response to MTX treatment and Vitamin B12 concentration individually, and in combination. Results: MTX treatment alone significantly increased LINE-1 methylation in SH-SY5Y (p = 0.040) and DAOY (p < 0.001), and increased FKBP5 methylation in MO3.13 cells (p = 0.009). Conclusion: We conclude that altered DNA methylation of brain/central nervous system cells could be one mechanism involved in MTX treatment-related neurotoxicities and neurocognitive late effects in ALL survivors.
Author(s): Forster VJ, McDonnell A, Theobald R, McKay JA
Publication type: Article
Publication status: Published
Online publication date: 15/08/2017
Acceptance date: 21/06/2017
Date deposited: 28/09/2017
ISSN (print): 1750-1911
ISSN (electronic): 1750-192X
Publisher: Future Medicine Ltd.
Altmetrics provided by Altmetric