Xenobiotic Receptor-Mediated Carcinogenesis

A variety of xenobiotics such as dioxin, peroxisome proliferators, hormones, and phorbol esters result in tumors without directly damaging DNA. Instead, these compounds are classified as tumor promoters and their mode of action includes affecting cellular proliferation, apoptosis, or differentiation. The manner in which the aforementioned chemicals affect cellular fate is by altering gene expression initiated by interacting with soluble, intracellular receptors. The targets of receptor-mediated carcinogens include nuclear hormone receptors, the aryl hydrocarbon receptor, protein kinase C (PKC), and protein phosphatase 2A. In this article, the structure, function, and regulation of these proteins, as well as the downstream events that result from tumor promoters interacting with their cognate receptor, are described.