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


METHODS
Wild-type and NQO2-null mice were exposed to 0, 1, and 3 Gy gamma-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 gamma-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.


CONCLUSIONS
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.
Iskander
Karim
K
Department of Pharmacology, Baylor College of Medicine, and Department of Pathology, Methodist Hospital, Houston, TX, USA.
Barrios
Roberto J
RJ
Jaiswal
Anil K
AK
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D011808:Quinone Reductases / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases