Carcinogenesis Advance Access published online on July 17, 2003
Carcinogenesis, doi:10.1093/carcin/bgg117
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Gastroenterology, University Medical Centre St Radboud, Nijmegen, The Netherlands
* Corresponding author. E-mail: w.peters{at}mdl.umcn.nl.
Received 5 February 2003
; revised 27 June 2003
; accepted 30 June 2003
Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which is associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, also several dietary compounds able to reduce gastrointestinal cancer rates both in humans and animals have been characterised. Though the exact mechanism leading to the anticarcinogenic action of these compounds is not fully known, it has been demonstrated that this chemopreventive capacity may be due to elevation of the glutathione S-transferase detoxification enzymes. Now we investigated the effect of several anticarcinogens on the gastrointestinal UDP-glucuronosyltransferase (UGT) enzymes. Diets of male Wistar rats were supplemented with ellagic acid, ferulic acid, Brussels sprouts, quercetin,
Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens
-angelicalactone, tannic acid, coumarin, fumaric acid, curcumin and flavone separately, and combinations of -angelicalactone and flavone. Hepatic and intestinal (proximal-, mid-, distal small intestine and colon) UGT enzyme activities were quantified by using 4-nitrophenol and 4-methylumbelliferone as substrates. All anticarcinogens tested increased UGT enzyme activity with both substrates, at least at one of the five different sites investigated. -Angelicalactone, coumarin and curcumin showed enhanced UGT enzyme activities at all five sites. Both small and large intestinal UGT enzyme activities were increased by quercetin, -angelicalactone, coumarin, curcumin and flavone. Except for tannic acid, all agents induced hepatic UGT enzyme activity. Furthermore, dietary administration of -angelicalactone and flavone, given individually or in combination, enhanced the UGT detoxification system in the liver and to a lesser extent in intestine. In conclusion, induction of gastrointestinal UGT enzyme activities after consumption of dietary anticarcinogens, may contribute to a better detoxification of potentially carcinogenic compounds and subsequently to the prevention of gastrointestinal cancer.
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