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Rompelberg, C.J.M. (author), Vogels, J.T.W.E. (author), de Vogel, N. (author), Bruijntjes-Rozier, G.C.D.M. (author), Stenhuis, W.H. (author), Bogaards, J.J.P. (author), Verhagen, H. (author), TNO Voeding (author)
1. In order to study the antigenotoxic potential of eugenol in humans, ten healthy non-smoking males ingested a daily amount of 150 mg eugenol or the placebo for seven consecutive days. After a washout period of one week, groups ingesting eugenol or the placebo were crossed and received the other treatment for seven consecutive days. 2. On days...
article 1996
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Hissink, A.M. (author), Oudshoorn, M.J. (author), van Ommen, B. (author), Haenen, G.R.M.M. (author), van Bladeren, P.J. (author)
The oxidative biotransformation of 1, 2-dichlorobenzene (1, 2-DCB) was investigated using hepatic microsomes from male Wistar, Fischer-344 and Sprague-Dawley (SD) rats, phenobarbital (PB)- and isoniazid (ISO) pretreated male Wistar rats and from man. In addition, microsomes from cell lines selectively expressing one cytochrome P450 (P4502E1, 1A1...
article 1996
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Soffers, A.E.M.F. (author), Ploemen, J.H.T.M. (author), Moonen, M.J.H. (author), Wobbes, T. (author), van Ommen, B. (author), Vervoort, J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)
Quantitative structure - activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes studied, the natural...
article 1996
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Bogaards, J.J.P. (author), Venekamp, J.C. (author), van Bladeren, P.J. (author)
The metabolism of isoprene was investigated with microsomes derived from cell lines expressing human CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, or CYP3A4. The formation of epoxide metabolites was determined by gas chromatographic analysis. CYP2E1 showed the highest rates of formation of the isoprene monoepoxides 3,4-epoxy-3-methyl-1...
article 1996
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Hissink, E. (author), van Ommen, B. (author), Bogaards, J.J. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
article 1996
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Lansink, M. (author), van Bennekum, A.M. (author), Blaner, W.S. (author), Kooistra, T. (author), TNO Preventie en Gezondheid (author)
Retinoic acid stimulates the expression of tissue-type plasminogen activator (t-PA) in vascular endothelial cells in vitro and enhances t-PA levels in plasma and tissues in vivo. Compared with the in vivo situation, high retinoic acid concentrations are required to induce optimally t-PA expression in vitro. These findings led us to study...
article 1997
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TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author), Hissink, A.M. (author), Oudshoorn, M.J. (author), van Ommen, B. (author), van Bladeren, P.J. (author)
Our goal was to characterize possible species and strain differences in the hepatic microsomal biotransformation of 1,4-dichlorobenzene (1,4-DCB). Experiments compared extent of labeled 1,4-DCB conversion to oxidized metabolites, glutathione conjugates, and covalently bound metabolites by hepatic microsomes from humans, from male B6C3F1 mice,...
article 1997
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Instituut CIVO-Toxicologie en Voeding TNO (author), van Engelen, J.G.M. (author), de Rebel-Haan, W. (author), Opdam, J.J.G. (author), Mulder, G.J. (author)
In order to study the effects of methyl ethyl ketone (MEK) on the toxicokinetics of n-hexane and, in particular, the formation of 2,5-hexanedione from n-hexane in humans, volunteers were exposed to n-hexane (approx. 60 ppm, 2.4 μM in the inhaled air) with or without simultaneous inhalatory coexposure to MEK for 15.5 min. The concentration-time...
article 1997
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Sherratt, P.J. (author), Manson, M.M. (author), Thomson, A.M. (author), Hissink, E.A.M. (author), Neal, G.E. (author), van Bladeren, P.J. (author), Green, T. (author), Hayes, J.D. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the...
article 1998
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van Iersel, M.L.P.S. (author), Cnubben, N.H.P. (author), Smink, N. (author), Koeman, J.H. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The cyclopentenone prostaglandin A2 (PGA2) is known to inhibit cell proliferation, and metabolism of this compound thus might be important in controlling its ultimate function. The glutathione-related metabolism of PGA2 was therefore investigated both with purified glutathione S-transferase P1-1 (GSTP1-1) and with IGR-39 human melanoma cells....
article 1999
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van Iersel, M.L.P.S. (author), Verhagen, H. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the (anti)carcinogenic potential of other compounds. This...
article 1999
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van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated...
article 2000
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Soffers, A.E.M.F. (author), Boersma, M.G. (author), Vaes, W.H.J. (author), Vervoort, J. (author), Tyrakowska, B. (author), Hermens, J.L.M. (author), Rietjens, I.M.C.M. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)
Over the past decades the description of quantitative structure-activity relationships (QSARs) has been undertaken in order to find predictive models and/or mechanistic explanations for chemical as well as biological activities. This includes QSAR studies in toxicology. In an approach beyond the classical QSAR approaches, attempts have been made...
article 2001
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Krul, C.A.M. (author), Humblot, C. (author), Philippe, C. (author), Vermeulen, M. (author), van Nuenen, M. (author), Havenaar, R. (author), Rabot, S. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
Cruciferous vegetables, such as Brassica, which contain substantial quantities of glucosinolates, have been suggested to possess anticarcinogenic activity. Cutting and chewing of cruciferous vegetables releases the thioglucosidase enzyme myrosinase, which degrades glucosinolates to isothiocyanates and other minor metabolites. Cooking of...
article 2002
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Cnubben, N.H.P. (author), Elliott, G.R. (author), Hakkert, B.C. (author), Meuling, W.J.A. (author), van de Sandt, J.J.M. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)
The validity of in vitro and in vivo methods for the prediction of percutaneous penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP) (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of...
article 2002
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Smith, R.L. (author), Adams, T.B. (author), Doull, J. (author), Feron, V.J. (author), Goodman, J.I. (author), Marnett, L.J. (author), Portoghese, P.S. (author), Waddell, W.J. (author), Wagner, B.M. (author), Rogers, A.E. (author), Caldwell, J. (author), Sipes, I.G. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)
This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data...
article 2002
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Wolken, W.A.M. (author), Tramper, J. (author), van der Werf, M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)
Many organisms have the ability to form spores, a remarkable phase in their life cycles. Compared with vegetative cells, spores have several advantages (e.g. resistance to toxic compounds, temperature, desiccation and radiation) making them well suited to various applications. The applications of spores that first spring to mind are bio-warfare...
article 2003
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Roza, L. (author), de Vogel, N. (author), van Delft, J.H.M. (author)
Hydroquinone (HQ) occurs in the environment as a result of manmade processes as well as in natural products from plants and animals. The compound has been reported to produce chromosomal effects in some in vivo and in vitro animal models. However, its potential to produce similar effects in human lymphocytes is less clear. To obtain more...
article 2003
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Blanquet, S. (author), Meunier, J.P. (author), Minekus, M. (author), Marol-Bonnin, S. (author), Alric, M. (author)
The use of genetically engineered microorganisms such as bacteria or yeasts as live vehicles to carry out bioconversion directly in the digestive environment is an important challenge for the development of innovative biodrugs. A system that mimics the human gastrointestinal tract was combined with a computer simulation to evaluate the survival...
article 2003
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Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Awad, H.M. (author), Boersma, M.G. (author), Brand, W. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Voeding (author)
In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1′-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1′-hydroxylation of safrole was characterized in a variety of in vitro test systems, including Supersomes, expressing...
article 2004
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