Table 1.

Key characteristics of carcinogens (from Smith et al. [6])

1. Is electrophilic or can be metabolically activated

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

2. Is genotoxic

DNA damage (DNA strand breaks, DNA protein cross-links, unscheduled DNA synthesis), intercalation, gene mutations, cytogenetic changes (e.g. chromosome aberrations, micronuclei)

3. Alters DNA repair or causes genomic instability

Alterations of DNA replication or repair (e.g. topoisomerase II, base-excision or double-strand break repair)

4. Induces epigenetic alterations

DNA methylation, histone modification, microRNA expression

5. Induces oxidative stress

Oxygen radicals, oxidative stress, oxidative damage to macromolecules (e.g. DNA, lipids)

6. Induces chronic inflammation

Elevated white blood cells, myeloperoxidase activity, altered cytokine and/or chemokine production

7. Is immunosuppressive

Decreased immunosurveillance, immune system dysfunction

8. Modulates receptor-mediated effects

Receptor in/activation (e.g. ER, PPAR, AhR) or modulation of exogenous ligands (including hormones)

9. Causes immortalization

Inhibition of senescence, cell transformation

10. Alters cell proliferation, cell death or nutrient supply

Increased proliferation, decreased apoptosis, changes in growth factors, energetics and signaling pathways related to cellular replication or cell cycle