title: Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines.
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.
authors.affiliation: Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Fekadu
authors.initials: F
authors.lastname: Kassie
authors.forename: Volker Mersch
authors.initials: VM
authors.lastname: Sundermann
authors.forename: R
authors.initials: R
authors.lastname: Edenharder
authors.forename: Karl L
authors.initials: KL
authors.lastname: Platt
authors.forename: F
authors.initials: F
authors.lastname: Darroudi
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lhoste
authors.forename: C
authors.initials: C
authors.lastname: Humbolt
authors.forename: Eva
authors.initials: E
authors.lastname: Muckel
authors.forename: Maria
authors.initials: M
authors.lastname: Uhl
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmüller
mesh_terms: D016588:Anticarcinogenic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D003110:Colonic Neoplasms / Q000517:prevention & control; D004032:Diet; D005504:Food Analysis; D006571:Heterocyclic Compounds / Q000037:antagonists & inhibitors*; D006801:Humans; D008113:Liver Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D006571:Heterocyclic Compounds