Alex McDonnell

• BSc (Hons) Biochemistry
• DNA methylation as a mediating mechanism in the development of neurotoxicity in response to multiple impacts on one carbon metabolism during methotrexate treatment.

DNA methylation is suspected to be one mechanism involved in treatment-related neurotoxicities presented in childhood leukaemia patients treated with both methotrexate and nitrous oxide. Said neurotoxicity manifests often as demyelination of the nervous system. Methotrexate and nitrous oxide both inhibit one carbon metabolism, and it’s suggested that changes in concentrations of one carbon metabolites may interact with methotrexate treatment to alter DNA methylation. Using one carbon metabolites as a proxy for nitrous oxide, we investigated the effects methotrexate had on the methylation of global and myelin-related genes in cells of oligodendrocyte origin.

Project Supervisor: Dr Jill McKay, Institute of Health & Society

Funding source: Rank Prize Fund