Fig 1.
Role of MTX in relation to one-carbon metabolism.
SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; DHF: dihydrofolate; THF: tetrahydrofolate; TS: thymidylate synthase; DHFR: dihydrofolate reductase; MTHFD1: methylenetetrahydrofolate dehydrogenase 1; MTHFR: methylenetetrahydrofolate reductase; MTX: methotrexate. Folic acid donates a methyl-group to the one-carbon metabolism pathway. Through several steps methionine is transformed into SAM, which then donates the methyl-group for the DNA methylation process, and is transformed into SAH and homocysteine. MTX inhibits DHFR and TS. By inhibiting DHFR, MTX inhibits the pathway leading to methylation.
Table 1.
Baseline characteristics (n = 82).
Table 2.
Methylation before and after stop of MTX therapy.
Table 3.
SAM and SAH levels and LINE1 DNA methylation in relation to MTX-induced oral mucositis.