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Publication : In vivo role of NAD(P)H:quinone oxidoreductase 1 in metabolic activation of mitomycin C and bone marrow cytotoxicity.

First Author  Adikesavan AK Year  2007
Journal  Cancer Res Volume  67
Issue  17 Pages  7966-71
PubMed ID  17804703 Mgi Jnum  J:124889
Mgi Id  MGI:3722738 Doi  10.1158/0008-5472.CAN-06-4480
Citation  Adikesavan AK, et al. (2007) In vivo Role of NAD(P)H:Quinone Oxidoreductase 1 in Metabolic Activation of Mitomycin C and Bone Marrow Cytotoxicity. Cancer Res 67(17):7966-71
abstractText  NAD(P)H:quinone oxidoreductase 1(-/-) (NQO1(-/-)), NQO1(+/-) along with NRH:quinone oxidoreductase 2(-/-) (NQO2(-/-)), and wild-type (WT) mice were exposed to five once weekly doses of mitomycin C. The mice were euthanized 15 weeks after the first dose. Blood cell counts and histologic analyses were done. WT and NQO2(-/-) mice showed hypocellularity and a significant increase in adipocytes in bone marrow. They also showed anemia because of the loss of RBC and hemoglobin. The neutrophils and platelets were reduced, whereas other blood cell types and tissues were normal. Interestingly, NQO1(-/-) mice showed a complete resistance to mitomycin C-induced bone marrow cytotoxicity and reduction in RBC, hemoglobin, and neutrophils. NQO1(+/-) mice also showed limited resistance to mitomycin C-induced bone marrow cytotoxicity. These data show a major in vivo role of NQO1 in metabolic activation of mitomycin C with implications in mitomycin C chemotherapy. [Cancer Res 2007;67(17):7966-71].
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