The Key Characteristics of Carcinogens

(Adapted from Smith et al. 2016, 2020)

Examples of relevant evidence

1. Is Electrophilic or Can Be Metabolically Activated

(Shì qīn diànzǐ de huò kěyǐ bèi dàixiè jīhuó)

Est électrophile ou peut être activé métaboliquement

Parent compound or metabolite with an electrophilic structure (e.g., epoxide, quinone, etc), formation of DNA and protein adducts.

2. Is Genotoxic

(Yǒu yíchuán dúxìng)

Est génotoxique

DNA damage (DNA strand breaks, DNA-protein cross-links, unscheduled DNA synthesis), intercalation, mutations/single nucleotide variants, structural and numerical chromosome alterations (clastogenicity/aneugenicity), cytogenetic changes (e.g., chromosome aberrations, micronuclei).
3. Alters DNA repair or causes genomic instabilityAlterations of DNA replication and repair capacity (e.g., topoisomerase II, base-excision or double-strand break repair); Copy number variations (duplications, deletions, amplifications, insertions), Inter-/intra-chromosomal translocations, Microsatellite instability, Increased expression of activation-induced cytidine deaminase (AICD).
4. Induces Epigenetic AlterationsGlobal and locus-specific DNA methylation, histone modifications, Chromatin remodeling, Changes in non-coding RNAs
5. Induces Oxidative StressReactive oxygen species (ROS) formation, oxidative damage to macromolecules (e.g., DNA, lipids), Glutathione depletion, NFE2L2-ARE-dependent gene expression response, Lipid peroxidation.
6. Induces chronic inflammationTissue inflammation, Inflammatory signaling.
7. Is ImmunosuppressiveDecreased immunosurveillance, immune system dysfunction, T cell activation and proliferation, Cytotoxic T-lymphocyte (CTL) activity, Natural killer cell activity.
8. Modulates receptor-mediated effectsInteracts with receptors, receptor activation, modulation of endogenous ligands (including hormones)
9. Causes ImmortalizationAltered cellular senescence markers, Modified in vitro cell transformation activity, Increases in telomere length and telomerase activity, Alterations in stem cell genes.
10. Alters cell proliferation, cell death or nutrient supply Increased proliferation, decreased apoptosis, changes in growth factors, alterations in signaling pathways related to cellular replication or cell cycle control, changes to energetics reflected as a glycolytic (Warburg) shift, angiogenesis.