A methionine-free diet associated with nitrosourea treatment down-regulates methylguanine-DNA methyl transferase activity in patients with metastatic cancer.
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.
Thivat
Emilie
E
Centre Jean Perrin, Unitt de Recherche Clinique, Clermont-Ferrand, France. Recherche.clinique@cjp.fr
Durando
Xavier
X
Demidem
Aïcha
A
Farges
Marie-Chantal
MC
Rapp
Maryse
M
Cellarier
Eric
E
Guenin
Samuel
S
D'Incan
Michel
M
Vasson
Marie-Paule
MP
Chollet
Philippe
P
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*
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C051263:N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea; D008715:Methionine; D019853:O(6)-Methylguanine-DNA Methyltransferase