NRH:Quinone oxidoreductase 2-deficient mice are highly susceptible to radiation-induced B-cell lymphomas

Karim Iskander, Roberto Barrios, Anil K. Jaiswal

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Purpose: NRH:quinone oxidoreductase 2 (NQO2) is known to protect against myelogenous hyperplasia. However, the role of NQO2 in prevention of hematologic malignancies remains unknown. Present studies investigated in vivo role of NQO2 in prevention of myeloproliferative disease and lymphomas. Experimental Design: Wild-type and NQO2-null mice were exposed to 0, 1, and 3 Gy γ-radiation. One year later, the mice were analyzed for the development of myeloproliferative disease and lymphomas. Immunohistochemistry analysis determined the B- and T-cell origin of lymphomas. The mice were also sacrificed at 6 and 48 h after radiation exposure and bone marrow was collected and analyzed for p53, Bax, and B-cell apoptosis. Bone marrow cells were cultured and the rate of degradation of p53 was analyzed. Results: Seventy-two percent NQO2-null mice showed development of B-cell lymphomas in multiple tissues compared with 11% in wild-type mice exposed to 3 Gy γ-radiation. In contrast, only 22% NQO2-null mice showed myeloproliferation compared with none in wild-type mice. Further analysis revealed that bone marrow from NQO2-null mice contained lower levels of p53 compared with wild-type mice due to rapid degradation of p53. In addition, the exposure to radiation resulted in lower induction of p53 and Bax and decreased B-cell apoptosis in NQO2-null mice. Conclusion: NQO2-null mice are highly susceptible to develop radiation-induced B-cell lymphomas. The lack of significant induction of p53 and Bax and decrease in B-cell apoptosis presumably contributed to the development of lymphomas. NQO2 functions as endogenous factor in prevention against radiation-induced B-cell lymphomas.

Original languageEnglish (US)
Pages (from-to)1534-1542
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number5
DOIs
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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