Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 347431
Title In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro
Author(s) Haan, L.H.J. de; Pot, G.K.; Aarts, J.M.M.J.G.; Rietjens, I.M.C.M.; Alink, G.M.
Source Toxicology in Vitro 20 (2006)5. - ISSN 0887-2333 - p. 594 - 600.
Department(s) Toxicology
Nutrition and Disease
Publication type Refereed Article in a scientific journal
Publication year 2006
Keyword(s) dt-diaphorase - menadione toxicity - quinone toxicity - human colon - cells - nqo1 - reductase - enzymes - lines - sensitivity
Abstract NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose¿response curve revealing a `lower protection threshold¿ of 0.5 ¿mol DCPIP/min/mg protein and an `upper protection threshold¿ at 1 ¿mol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I3C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed `lower protection threshold¿ in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this `lower protection threshold¿ will require 5¿20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds
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