NAD(P)H: quinone oxidoreductase 1 expression in human bone marrow endothelial cells

NAD(P)H:quinone oxidoreductase 1 (NQO1) participates in the detoxification of many environmental quinones and related compounds. Recent studies have s uggested that individuals with a polymorphism in NQO1 (NQO1*2), which resul ts in a decrease (heterozygous, NQO1*1/*2) or a total loss (homozygous, NQO 1*2/*2) of NQO1, may be at increased risk for the development of leukemias. Previous studies have failed to detect NQO1 in freshly aspirated bone marr ow including Ficoll-purified mononuclear cells and purified CD34(+) hematop oietic progenitor stem cells. In these studies we examined human bone marro w core biopsies by immunohistochemistry using monoclonal antibodies directe d against NQO1. These studies revealed that NQO1 was expressed in human bon e marrow but expression of NQO1 was limited to bone marrow endothelium and adipocytes. To confirm the expression of NQO1 in bone marrow endothelial ce lls we examined an immortalized human bone marrow endothelial cell line (HB MEC-60) for NQO1 protein expression. Immunoblot analysis and an activity as say confirmed the expression of NQO1 in HBMEC-60. These data demonstrate th at NQO1 is present in human bone marrow. The increased risk of leukemia ass ociated with a deficit in NQO1 levels due to the NQO1*2 polymorphism may re flect impaired quinone detoxification and an increased susceptibility of en dothelial cells in bone marrow to environmental insults. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.