Hartwig2020_Article_ModeOfAction-basedRiskAssessme.pdf 3,42MB
1000 Titel
  • Mode of action-based risk assessment of genotoxic carcinogens
1000 Autor/in
  1. Hartwig, Andrea |
  2. Arand, Michael |
  3. Epe, Bernd |
  4. Guth, Sabine |
  5. Jahnke, Gunnar |
  6. Lampen, Alfonso |
  7. Martus, Hans-Jörg |
  8. Monien, Bernhard |
  9. Rietjens, Ivonne M. C. M. |
  10. Schmitz-Spanke, Simone |
  11. Schriever-Schwemmer, Gerlinde |
  12. Steinberg, Pablo |
  13. Eisenbrand, Gerhard |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-15
1000 Erschienen in
1000 Quellenangabe
  • 94:1787-1877
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B1, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.
1000 Sacherschließung
lokal Endogenous exposure
lokal Mode of action
lokal Genotoxicity
lokal Exogenous exposure
lokal Carcinogens
lokal Risk assessment
lokal Toxicogenomics
lokal Biomarker dosimetry
lokal Mutagens
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Hinweis
  • A Letter to the Editor, News and Views to this article was published on 07 September 2020 ( ; A Correction to this article was published on 22 July 2020 ( ; A Letter to the Editor, News and Views to this article was published on 17 July 2020 ( ; This article has been updated (
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. HA2372/4-15; LA1177/12-1; STE493/18-10
1000 Förderprogramm
  1. -
1000 Dateien
  1. Mode of action-based risk assessment of genotoxic carcinogens
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer HA2372/4-15; LA1177/12-1; STE493/18-10
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6423248.rdf
1000 Erstellt am 2020-10-01T13:45:47.236+0200
1000 Erstellt von 254
1000 beschreibt frl:6423248
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Fri May 13 18:49:29 CEST 2022
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1000 Vgl. frl:6423248
1000 Oai Id
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