title: Irradiation-induced p53 expression is attenuated in cells with NQO1 C465T polymorphism.
abstract: NAD(P)H:quinone acceptor oxidoreductase (NQO) 1 polymorphism is associated with various hematological malignancies, especially infant leukemia or therapy-related leukemias, which involve the rearrangement of mixed lineage leukemia (MLL) gene. Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (EBV-LCLs) with either of 2 well known polymorphic variations of C609T and C465T were selected from our archives of EBV-LCL clones and studied the induction of p53 expression after DNA damage. Irradiation of cells with C609T/C609T polymorphism (NQO1 *2*2) did not affect the induction of p53 expression. However, irradiation of cells with C465T/WT polymorphism (NQO1 *1*3) resulted in attenuation of p53 and p21 induction. Our results suggest that increased risk of infant leukemia development in patients with NQO1 *1*3 polymorphism is partially dependent on the inhibition of p53 pathway, though further studies are needed to fully understand the pathological role of C465T variant in the development of childhood leukemia.
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D019943:Amino Acid Substitution; D015153:Blotting, Western; D002461:Cell Line, Transformed / Q000528:radiation effects; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D020125:Mutation, Missense; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; D051788:Myeloid-Lymphoid Leukemia Protein; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D015689:Oncogene Protein p21(ras)