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. 2020 Jun 16;8:307. doi: 10.3389/fped.2020.00307

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Copyright © 2020 Cwiklinska, Czogala, Kwiecinska, Madetko-Talowska, Szafarz, Pawinska, Wieczorek, Klekawka, Rej, Stepien, Halubiec, Lazarczyk, Miklusiak, Bik-Multanowski, Balwierz and Skoczen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The presentation of intracellular methotrexate metabolism pathways. Factors that may be responsible for the inconsistency among studies assessing the role of SLC19A1/TS/MTHFR polymorphisms in methotrexate toxicity are marked with an asterisk (*).5,10-mTHF, 5,10-methylenetetrahydrofolate; ABC, ATP-binding cassette; DHFR, dihydrofolate reductase; FPGS, folylpolyglutamate synthase; GGH, γ-glutamyl transferase; miR-595, micro RNA 595; MTHFR, methylenetetrahydrofolate reductase; Mtx, methotrexate; OATP1A/1B, organic anion–transporting polypeptides 1A/1B; p53, p53 protein; SLC19A1, solute carrier family 19 member 1; TS, thymidylate synthase.