Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines

Fekadu Kassie, Volker Mersch Sundermann, R. Edenharder, Karl L. Platt, F. Darroudi, Evelyne Lhoste, C. Humbolt, Eva Muckel, Maria Uhl, Michael Kundi, Siegfried Knasmüller

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

This article describes the development and use of assay models in vitro (genotoxicity assay with genetically engineered cells and human hepatoma (HepG2) cells) and in vivo (genotoxicity and short-term carcinogenicity assays with rodents) for the identification of dietary constituents which protect against the genotoxic and carcinogenic effects of heterocyclic aromatic amines (HAs). The use of genetically engineered cells expressing enzymes responsible for the bioactivation of HAs enables the detection of dietary factors that inhibit the metabolic activation of HAs. Human derived hepatoma (HepG2) cells are sensitive towards HAs and express several enzymes [glutathione S-transferase (GST), N-acetyltransferase (NAT), sulfotransferase (SULT), UDP-glucuronosyltransferase (UDPGT), and cytochrome P450 isozymes] involved in the biotransformation of HAs. Hence these cells may reflect protective effects, which are due to inhibition of activating enzymes and/or induction of detoxifying enzymes. The SCGE assay with rodent cells has the advantage that HA-induced DNA damage can be monitored in a variety of organs which are targets for tumor induction by HAs. ACF and GST-P+ foci constitute preneoplastic lesions that may develop into tumors. Therefore, agents that prevent the formation of these lesions may be anticarcinogens. The foci yield and the sensitivity of the system could be substantially increased by using a modified diet. The predictive value of the different in vitro and in vivo assays described here for the identification of HA-protective dietary substances relevant for humans is probably better than that of conventional in vitro test methods with enzyme homogenates. Nevertheless, the new test methods are not without shortcomings and these issues are critically discussed in the present article.

Original languageEnglish (US)
Pages (from-to)183-192
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume523-524
DOIs
StatePublished - 2003

Bibliographical note

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • Chemoprevention
  • Heterocyclic amines
  • Test methods

Fingerprint Dive into the research topics of 'Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines'. Together they form a unique fingerprint.

Cite this