International Journal of Molecular Sciences

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Dear Colleagues,

There is a regulatory gap in addressing the hazard assessment of Non Genotoxic Carcinogenic Chemicals to better protect public health for many product and regulatory sectors, and alternative mechanistic based approaches are needed to address this gap.

This Special Issue is a continuation of previous issue and will focus on recent advances in the hazard assessment of non genotoxic carcinogenic (NGTxC) chemicals and will include papers on:

Assay developments and chemicals screened that plausibly address relevant mechanisms and modes of action, including: ADME; Immune response and inflammatory biomarkers, and specifically measurement of cytokine release; Cytoskeleton modification, to discriminate between adaptive to the adverse response; Cancer specific kinase activation; 3D models that can genuinely address the complexity at the tissue level that the individual cell based molecular based assays cannot address.
Relevant quantitative and qualitative pathway based approaches for NGTxC.
Applications of molecular targets from human clinical data for mechanistic understanding of key biomarkers in the carcinogenesis process.
Discussion on human relevance of mechanisms and modes of action. For example rodent CAR/PXR and peroxisome proliferation/PPARs induction in liver tumours are generally dismissed as not being human relevant, but looking more holistically, is this really the case?
Potentiation effects of viruses on chemical non genotoxic carcinogenicity.

We warmly welcome submissions, including original papers and reviews, on these topical needs.

Dr. Miriam N. Jacobs
Prof. Dr. Annamaria Colacci
Guest Editors

Manuscript Submission Information

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Related Special Issue

Published Papers (1 paper)

Review

24 pages, 4763 KiB

Open AccessReview

Increased Cell Proliferation as a Key Event in Chemical Carcinogenesis: Application in an Integrated Approach for the Testing and Assessment of Non-Genotoxic Carcinogenesis

by Christian Strupp, Marco Corvaro, Samuel M. Cohen, J. Christopher Corton, Kumiko Ogawa, Lysiane Richert and Miriam N. Jacobs

Int. J. Mol. Sci. 2023, 24(17), 13246; https://doi.org/10.3390/ijms241713246 - 26 Aug 2023

Cited by 2 | Viewed by 1166

Abstract

In contrast to genotoxic carcinogens, there are currently no internationally agreed upon regulatory tools for identifying non-genotoxic carcinogens of human relevance. The rodent cancer bioassay is only used in certain regulatory sectors and is criticized for its limited predictive power for human cancer risk. Cancer is due to genetic errors occurring in single cells. The risk of cancer is higher when there is an increase in the number of errors per replication (genotoxic agents) or in the number of replications (cell proliferation-inducing agents). The default regulatory approach for genotoxic agents whereby no threshold is set is reasonably conservative. However, non-genotoxic carcinogens cannot be regulated in the same way since increased cell proliferation has a clear threshold. An integrated approach for the testing and assessment (IATA) of non-genotoxic carcinogens is under development at the OECD, considering learnings from the regulatory assessment of data-rich substances such as agrochemicals. The aim is to achieve an endorsed IATA that predicts human cancer better than the rodent cancer bioassay, using methodologies that equally or better protect human health and are superior from the view of animal welfare/efficiency. This paper describes the technical opportunities available to assess cell proliferation as the central gateway of an IATA for non-genotoxic carcinogenicity. Full article

(This article belongs to the Special Issue Advances in Mechanism Based Toxicity and Hazard Assessment of NGTxC Chemicals 2.0)

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