AUTHOR=Cohen Samuel M. 

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

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1394584

DOI=10.3389/fonc.2024.1394584

ISSN=2234-943X

ABSTRACT=<p>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 <italic>in silico</italic>, <italic>in vitro</italic>, and short-term <italic>in vivo</italic> 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.</p>