Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge

Douglas C. Wolf, Samuel M. Cohen, Alan R. Boobis, Vicki L. Dellarco, Penelope A. Fenner-Crisp, Angelo Moretto, Timothy P. Pastoor, Rita S. Schoeny, Jennifer G. Seed, John E. Doe

Research output: Contribution to journalComment/debatepeer-review

58 Scopus citations


Developments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from cell proliferation especially if sustained. Chemicals that act via direct interaction with DNA can induce cancer because they cause mutations which can be carried forward in dividing cells. Chemicals that act via non-genotoxic mechanisms must be dosed to maintain a proliferative environment so that the steps toward neoplasia have time to occur. Chemicals that induce increased cellular proliferation can be divided into two categories: those which act by a cellular receptor to induce cellular proliferation, and those which act via non-specific mechanisms such as cytotoxicity. This knowledge has implications for testing chemicals for carcinogenic potential and risk management.

Original languageEnglish (US)
Pages (from-to)86-92
Number of pages7
JournalRegulatory Toxicology and Pharmacology
StatePublished - Apr 2019


  • Carcinogenicity
  • Mode of action
  • Risk assessment

ASJC Scopus subject areas

  • Toxicology


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