title: A methionine-free diet associated with nitrosourea treatment down-regulates methylguanine-DNA methyl transferase activity in patients with metastatic cancer.
abstract: BACKGROUND
  Methionine (MET) depletion used in association with chemotherapy improves the therapeutic index in animal models. This potentiating effect may be due to tumor cell sensitization to chloroethylnitrosoureas through their MET dependency and the down-regulation of O6- methylguanine-DNA methyltransferase (MGMT). Our purpose was to evaluate the impact of the association of a dietary MET restriction with nitrosourea treatment on MGMT activity in peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  Six patients with metastatic cancer (melanoma and glioma) received 4 cycles of a MET-free diet with cystemustine (60 mg/m2).
  
  
  RESULTS
  MGMT activity in PBMCs decreased by an average of 13% from 553+/-90 fnol/mg before the diet to 413+/-59 fmol/mg after the diet + chemotherapy period (p=0.029). The decrease of MGMT activity was not affected by the duration of the MET-free diet period but seems to be correlated to the plasma MET depletion induced by the MET-free diet.
authors: Centre Jean Perrin, Unitt de Recherche Clinique, Clermont-Ferrand, France. Recherche.clinique@cjp.fr
authors: Emilie
authors: E
authors: Thivat
authors: Xavier
authors: X
authors: Durando
authors: Aïcha
authors: A
authors: Demidem
authors: Marie-Chantal
authors: MC
authors: Farges
authors: Maryse
authors: M
authors: Rapp
authors: Eric
authors: E
authors: Cellarier
authors: Samuel
authors: S
authors: Guenin
authors: Michel
authors: M
authors: D'Incan
authors: Marie-Paule
authors: MP
authors: Vasson
authors: Philippe
authors: P
authors: Chollet
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000201:enzymology / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D004032:Diet; D015536:Down-Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008545:Melanoma / Q000097:blood / Q000201:enzymology / Q000556:secondary / Q000628:therapy*; D008715:Methionine / Q000097:blood / Q000172:deficiency*; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000097:blood*; D009837:Oligodendroglioma / Q000201:enzymology / Q000556:secondary / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C051263:N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea; D008715:Methionine; D019853:O(6)-Methylguanine-DNA Methyltransferase