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

Karim Iskander, Roberto J. Barrios, Anil K. Jaiswal

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

NAD(P)H:quinone oxidoreductase 1 null (NQO1-/-) mice exposed to 3 Gy of γ-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 ofinf ection in mice. These results suggested that exposure ofN QO1-/- mice to γ-radiation led to myeloproliferative disease. Radiation-induced myeloproliferative disease was observed in 74% ofNQO1-/- mice as compared with none in wild-type (WT) mice. NQO1-/- mice exposed to γ-radiation also showed lymphoma tissues (32%) and lung adenocarcinoma (84%). In contrast, only 11% WT mice showed lymphoma and none showed lung adenocarcinoma. Exposure ofNQO1-/- mice to γ-radiation resulted in reduced apoptosis in granulocytes and lack ofinduction of p53, p21, and Bax. NQO1-/- mice also showed increased expression of myeloid differentiation factors CCAAT/enhancer binding protein α (C/EBPα) and Pu.1. Intriguingly, exposure of NQO1-/- mice to γ-radiation failed to induce C/EBPα and Pu.1, as was observed in WT mice. These results suggest that decreased p53/apoptosis and increased Pu.1 and C/EBPα led to myeloid hyperplasia in NQO1-/- mice. The lack of induction ofapoptos is and differentiation contributed to radiation-induced myeloproliferative disease in NQO1-/- mice.

Original languageEnglish (US)
Pages (from-to)7915-7922
Number of pages8
JournalCancer research
Volume68
Issue number19
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Disruption of NAD(P)H:Quinone oxidoreductase 1 gene in mice leads to radiation-induced myeloproliferative disease'. Together they form a unique fingerprint.

Cite this