Carcinogens are classified according to their mode of action as genotoxic or nongenotoxic carcinogens. Genotoxic carcinogens initiate carcinogenesis by direct interaction with DNA, resulting in DNA damage or chromosomal aberrations that can be detected by genotoxicity tests (OECD, 2006). Nongenotoxic carcinogens are agents that do not directly interact with DNA and are believed to enhance tumor development by affecting gene expression, signal transduction, and/or cell proliferation. In animal studies, most potent mutagens are also found to be carcinogenic (Maurici, et al., 2005, p. 177). Substances that induce tumors in animals are considered as presumed or suspected human carcinogens until convincing evidence to the contrary is presented (UNECE, 2004, p. 167).
Avila AM, Bebenek I, Bonzo JA, Bourcier T, Davis Bruno KL, Carlson DB, Dubinion J, Elayan I, Harrouk W, Lee SL, Mendrick DL, Merrill JC, Peretz J, Place E, Saulnier M, Wange RL, Yao J, Zhao D, Brown PC. An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs). Regul Toxicol Pharmacol. 2020 Jul;114:104662. doi: 10.1016/j.yrtph.2020.104662. Epub 2020 Apr 20. PMID: 32325112.