You are here:
RESPONSE TO KLAUNIG, J.E. ET AL, EPIGENETIC MECHANISMS OF CHEMICAL CARCINOGENESIS
Citation:
Preston, R J. RESPONSE TO KLAUNIG, J.E. ET AL, EPIGENETIC MECHANISMS OF CHEMICAL CARCINOGENESIS. HUMAN AND EXPERIMENTAL TOXICOLOGY. Co-published in Belle Newsletter, 19:569-570, (2000).
Description:
The article by Klaunig et al. is a comprehensive review of the general principles underlying the induction of tumors by epigenetic mechanisms. The review describes the roles of cell proliferation, loss of apoptotic function, gap junctional intercellular communication, P450 induction, oxidative stress, and altered gene expression in carcinogenesis. Further, it places these processes in the context of the dose-response relationship for "nongenotoxic" chemical carcinogenesis. Thus, it leads the reader through the cancer paradigm of induction, promotion, and progression where the drivers of the process are chemicals that do not directly interact with DNA.
I would like to consider this as the jumping off point for entry into a new and different approach for considering the framework for the production of cancer as elegantly reviewed and conceptualized in a recent review by Hanahan and Weinberg. In the terms described by these authors, the review by Klaunig et al. would be considered to present the reductionist view of cancer as opposed to the heterotypic cell biology view of cancer. It is proposed that although considerable progress has been made based upon the former view, the way forward is through the latter approach. In the heterotypic cell biology view of cancer, tumors are regarded as "complex tissues in which mutant cancer cells have conscripted and subverted normal cell types to serve as active collaborators in their neoplastic agenda". Such a model allows for the complex biology of the total cell to be taken into account when seeking perturbations as a result of an exposure to a chemical carcinogen, for example, be it genotoxic or epigenetic.