A feasibility study: Can information collected to classify for mutagenicity be informative in predicting carcinogenicity?

Regulatory Toxicology and Pharmacology : RTP
Petko I PetkovOvanes Mekenyan

Abstract

Carcinogenicity is a complex endpoint of high concern yet the rodent bioassay still used is costly to run in terms of time, money and animals. Therefore carcinogenicity has been the subject of many different efforts to both develop short-term tests and non-testing approaches capable of predicting genotoxic carcinogenic potential. In our previous publication (Mekenyan et al., 2012) we presented an in vitro-in vivo extrapolation workflow to help investigate the differences between in vitro and in vivo genotoxicity tests. The outcomes facilitated the development of new (Q)SAR models and for directing testing. Here we have refined this workflow by grouping specific tests together on the basis of their ability to detect DNA and/or protein damage at different levels of biological organization. This revised workflow, akin to an Integrated Approach to Testing and Assessment (IATA) informed by mechanistic understanding was helpful in rationalizing inconsistent study outcomes and categorizing a test set of carcinogens with mutagenicity data on the basis of regulatory mutagenicity classifications. Rodent genotoxic carcinogens were found to be correctly predicted with a high sensitivity (90-100%) and a low rate of false positives (3-10%). ...Continue Reading

References

Aug 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·B N AmesF D Lee
Dec 13, 2000·Mutation Research·K Mortelmans, E Zeiger
Dec 13, 2000·Mutation Research·J Clements
Dec 13, 2000·Mutation Research·T NohmiK Masumura
Nov 20, 2002·Mutation Research·Kerry L DearfieldUNKNOWN US Environmental Protection Agency
Aug 6, 2005·Mutation Research·Iain B LambertGeorge R Douglas
Apr 5, 2007·Nature Protocols·Peggy L Olive, Judit P Banáth
Sep 8, 2010·Environmental Toxicology and Chemistry·Gerald T AnkleyDaniel L Villeneuve
Oct 1, 2013·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Romualdo BenigniOlga Tcheremenskaia
Sep 28, 2014·Regulatory Toxicology and Pharmacology : RTP·Knut Erik TollefsenGrace Patlewicz

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Citations

May 25, 2015·Regulatory Toxicology and Pharmacology : RTP·T W SchultzM T D Cronin
May 27, 2016·Journal of Applied Toxicology : JAT·Petko I PetkovOvanes G Mekenyan
Jul 25, 2019·Frontiers in Chemistry·Toshihide Takeshita, Robert A Kanaly

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