Journal of Medical and Dental Sciences
Online ISSN : 2185-9132
Print ISSN : 1342-8810
ISSN-L : 1342-8810
Irradiation-induced p53 expression is attenuated in cells with NQO1 C465T polymorphism
Masaki SatoMasatoshi Takagi Shuki Mizutani
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JOURNAL OPEN ACCESS

2010 Volume 57 Issue 2 Pages 139-145

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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 (EBVLCLs) 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.
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© 2010 Tokyo Medical and Dental University (TMDU)
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