Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1999 Jun;12(6):467-75.
doi: 10.1021/tx9800811.

Modulation of the toxicity and macromolecular binding of benzene metabolites by NAD(P)H:Quinone oxidoreductase in transfected HL-60 cells

J Wiemels  1 , J K Wiencke, A Varykoni, M T Smith
Affiliations

Modulation of the toxicity and macromolecular binding of benzene metabolites by NAD(P)H:Quinone oxidoreductase in transfected HL-60 cells

J Wiemels et al. Chem Res Toxicol. 1999 Jun.

Abstract

Benzene is oxidized in the liver to produce a series of hydroxylated metabolites, including hydroquinone and 1,2,4-benzenetriol. These metabolites are activated to toxic and genotoxic species in the bone marrow via oxidation by myeloperoxidase (MPO). NAD(P)H:quinone oxidoreductase (NQO1) is an enzyme capable of reducing the oxidized quinone metabolites and thereby potentially reducing their toxicities. We introduced the NQO1 gene into the HL-60 cell line to create a high MPO-, high NQO1-expressing cell line, and tested its response in assays of benzene metabolite toxicity. NQO1 expression reduced a class of hydroquinone- and benzenetriol-induced DNA adducts by 79-86%. The cytotoxicity and apoptosis caused by hydroquinone were modestly reduced, while protein binding was unchanged and the rate of glutathione depletion increased. NQO1's activity in reducing a class of benzene metabolite-induced DNA adducts may be related to its known activities in maintaining membrane-bound endogenous antioxidants in reduced form. Alternatively, NQO1 activity may prevent the formation of adducts which result from polymerized products of the quinones. In either case, this protection by NQO1 may be an important mechanism in the observation that a lack of NQO1 activity affords an increased risk of benzene poisoning in exposed individuals [Rothman, N., et al. (1997) Cancer Res. 57, 2839-2842].

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

Publication types

LinkOut - more resources