Disruption of NAD(P)H:Quinone oxidoreductase 1 gene in mice leads to radiation-induced myeloproliferative disease Academic Article uri icon

Overview

MeSH Major

  • Genetic Predisposition to Disease
  • Myeloproliferative Disorders
  • NADPH Dehydrogenase
  • Radiation Injuries

abstract

  • NAD(P)H:quinone oxidoreductase 1 null (NQO1(-/-)) mice exposed to 3 Gy of gamma-radiation showed an increase in neutrophils, bone marrow hypercellularity, and enlarged lymph nodes and spleen. The spleen showed disrupted follicular structure, loss of red pulp, and granulocyte and megakarocyte invasion. Blood and histologic analysis did not show any sign of infection in mice. These results suggested that exposure of NQO1(-/-) mice to gamma-radiation led to myeloproliferative disease. Radiation-induced myeloproliferative disease was observed in 74% of NQO1(-/-) mice as compared with none in wild-type (WT) mice. NQO1(-/-) mice exposed to gamma-radiation also showed lymphoma tissues (32%) and lung adenocarcinoma (84%). In contrast, only 11% WT mice showed lymphoma and none showed lung adenocarcinoma. Exposure of NQO1(-/-) mice to gamma-radiation resulted in reduced apoptosis in granulocytes and lack of induction of p53, p21, and Bax. NQO1(-/-) mice also showed increased expression of myeloid differentiation factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and Pu.1. Intriguingly, exposure of NQO1(-/-) mice to gamma-radiation failed to induce C/EBPalpha and Pu.1, as was observed in WT mice. These results suggest that decreased p53/apoptosis and increased Pu.1 and C/EBPalpha led to myeloid hyperplasia in NQO1(-/-) mice. The lack of induction of apoptosis and differentiation contributed to radiation-induced myeloproliferative disease in NQO1(-/-) mice.

publication date

  • October 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2597166

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-08-0766

PubMed ID

  • 18829548

Additional Document Info

start page

  • 7915

end page

  • 22

volume

  • 68

number

  • 19