New models for assessing carcinogenesis: an ongoing process

Toxicology Letters
R C SillsM L Cunningham

Abstract

Traditionally, the use of rodent models in assessing the carcinogenic potential of chemicals has been expensive and lengthy, and the relevance of the carcinogenic effect to humans is often not fully understood. Today, however, with the rapid advances in molecular biology, genetically altered mice containing genes relevant to humans (e.g. oncogenes, tumor suppressor genes) and reporter genes (e.g. lacI) provide powerful tools for examining specific chemical-gene interactions thereby allowing a better understanding of the mechanisms of carcinogenesis in a shorter period of time. This paper will cover an overview of ongoing validation efforts, followed by examples of studies using several genetically engineered models including the p53def mouse model and the Big Blue transgenic mouse model. Specifically, examples where transgenic models were integrated into the testing program based on specific hypotheses dealing with genetic alterations in cancer genes and reporter genes will be discussed. The examples will highlight possible ways genetically altered mice may be integrated into a comprehensive research and testing strategy and thereby provide an improved estimation of human health risks.

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Citations

Jul 24, 2003·Toxicon : Official Journal of the International Society on Toxinology·P-J Senogles-DerhamM Shahin
Aug 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Astrid RohrbeckJuergen Borlak
Jul 26, 2008·Molecular Nutrition & Food Research·Giulia ChiesaCesare R Sirtori
Mar 17, 2015·Mutation Research·Sarah J Swerdlow, Roel M Schaaper
Aug 30, 2013·Critical Reviews in Toxicology·David A EastmondBabasaheb Sonawane
Jan 19, 2016·Molecular Nutrition & Food Research·Henry J ThompsonAnne McTiernan
Nov 6, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Heidrun Ellinger-ZiegelbauerHans-Jurgen Ahr
Jan 7, 2003·Toxicologic Pathology·Michelle Embree-Ku, Kim Boekelheide
Dec 11, 2007·Anais Da Academia Brasileira De Ciências·Paula A OliveiraCarlos Lopes

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