title: Scientific and Regulatory Policy Committee (SRPC) Review: Interpretation and Use of Cell Proliferation Data in Cancer Risk Assessment.
abstract: Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardization of proliferation assays will become an increasingly important part of cancer risk assessment. To help address this development, we also discuss the potential role for proliferation data as a component of alternative carcinogenicity testing models. This information should improve consistency of cell proliferation methods and increase efficiency of targeted testing strategies.
authors.affiliation: U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA wood.charles@epa.gov.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.affiliation: The Dow Chemical Company, Midland, Michigan, USA.
authors.forename: Renee R
authors.initials: RR
authors.lastname: Hukkanen
authors.affiliation: The Dow Chemical Company, Midland, Michigan, USA.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Sura
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA Current Affiliation: NDA Partners, LLC, Rochelle, Virginia, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jacobson-Kram
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co., KG Development, Biberach an der Riss, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nolte
authors.affiliation: Roche Diagnostics GmbH, PLBT, Penzberg, Germany.
authors.forename: Marielle
authors.initials: M
authors.lastname: Odin
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D009369:Neoplasms / Q000175:diagnosis* / Q000453:epidemiology*; D011786:Quality Control; D012015:Reference Standards; D012107:Research Design; D018570:Risk Assessment / Q000592:standards*
chemical_list: D002273:Carcinogens
keywords: BrdU; Ki-67; PCNA.; carcinogenesis; cell proliferation; mode of action