Cell proliferation and carcinogenesis: an approach to screening for potential human carcinogens

• Published in: Frontiers in oncology Vol. 14; p. 1394584
• Main Author: Cohen, Samuel M.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.05.2024
• Subjects: cytotoxicity; estrogenic activity; immunosuppression; mutagenesis; Oncology; regenerative proliferation; two-year bioassay; cell proliferation; immunosuppression; estrogenic activity; regenerative proliferation; mutagenesis; cytotoxicity; two-year bioassay
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2024.1394584

Cancer arises from multiple genetic errors occurring in a single stem cell (clonality). Every time DNA replicates, mistakes occur. Thus, agents can increase the risk of cancer either by directly damaging DNA (DNA-reactive carcinogens) or increasing the number of DNA replications (increased cell proliferation). Increased cell proliferation can be achieved either by direct mitogenesis or cytotoxicity with regenerative proliferation. Human carcinogens have a mode of action of DNA reactivity, immunomodulation (mostly immunosuppression), increased estrogenic activity (mitogenesis), or cytotoxicity and regeneration. By focusing on screening for these four effects utilizing in silico , in vitro , and short-term in vivo assays, a biologically based screening for human chemical carcinogens can be accomplished with greater predictivity than the traditional 2-year bioassay with considerably less cost, less time, and the use of fewer animals.