RT Book, Section A1 Glick, Adam B. A1 Dlugosz, Andrzej A. A2 Goldsmith, Lowell A. A2 Katz, Stephen I. A2 Gilchrest, Barbara A. A2 Paller, Amy S. A2 Leffell, David J. A2 Wolff, Klaus SR Print(0) ID 56057554 T1 Chapter 111. Chemical Carcinogenesis T2 Fitzpatrick's Dermatology in General Medicine, 8e YR 2012 FD 2012 PB The McGraw-Hill Companies PP New York, NY SN 978-0-07-166904-7 LK accessmedicine.mhmedical.com/content.aspx?aid=56057554 RD 2024/03/28 AB |PrintChemical Carcinogenesis at a GlanceIn 1775, Sir Percivall Pott's report of scrotal cancer in chimney sweeps established a link between environmental exposure and cutaneous malignancy.Over 200 chemicals have been linked to human cancer development, according to the National Toxicology Program's 11th Report on Carcinogens (2005).Chemicals implicated in human skin cancer development include polycyclic aromatic hydrocarbons and arsenic.Studies in mouse skin have defined operational stages of epithelial carcinogenesis: initiation, promotion, and malignant progression. Chemicals linked to human cancer are classified as tumor initiators, promoters, or “complete” carcinogens.Tumor initiation, associated with gene mutations that permanently alter the cell's biological responsiveness, is irreversible; tumor promotion a nonmutagenic process that provides a selective growth advantage to initiated cells, is reversible at early stages; agents that facilitate malignant progression are generally genotoxic.Most carcinogens must undergo metabolic activation, which involves enzymes involved in xenobiotic metabolism, including cytochrome p450 enzymes and glutathione S-transferase.An individual's likelihood of developing chemically induced skin cancer is a function of exposure history; presence of additional risk factors (e.g., UV exposure); and genetic background, including gene polymorphisms that influence susceptibility.