title: Effect of high-dose methotrexate on plasma hypoxanthine and uridine levels in patients with acute leukemia or non-Hodgkin lymphoma in childhood.
abstract: We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.
authors.affiliation: Department of Pediatrics, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Kasai
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: S
authors.initials: S
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D000293:Adolescent; D002648:Child; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D014529:Uridine / Q000097:blood*
chemical_list: D007042:Hypoxanthines; D019271:Hypoxanthine; D014529:Uridine; D008727:Methotrexate