Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8456288 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2016 | 24 Pages |
Abstract
Although in vitro chromosomal aberration tests and micronucleus tests have been widely used for genotoxicity evaluation, false-positive results have been reported under strong cytotoxic conditions. To reduce false-positive results, the new Organization for Economic Co-operation and Development (OECD) test guideline (TG) recommends the use of a new cytotoxicity index, relative increase in cell count or relative population doubling (RICC/RPD), instead of the traditionally used index, relative cell count (RCC). Although the use of the RICC/RPD may result in different outcomes and require re-evaluation of tested substances, it is impractical to re-evaluate all existing data. Therefore, we established a method to estimate test results from existing RCC data. First, we developed formulae to estimate RICC/RPD from RCC without cell counts by considering cell doubling time and experiment time. Next, the accuracy of the cytotoxicity index transformation formulae was verified by comparing estimated RICC/RPD and measured RICC/RPD for 3 major chemicals associated with false-positive genotoxicity test results: ethyl acrylate, eugenol and p-nitrophenol. Moreover, 25 compounds with false-positive in vitro chromosomal aberration (CA) test results were re-evaluated to establish a retrospective evaluation method based on derived estimated RICC/RPD values. The estimated RICC/RPD values were in good agreement with the measured RICC/RPD values for every concentration and chemical, and the estimated RICC suggested the possibility that 12 chemicals (48%) with previously judged false-positive results in fact had negative results. Our method enables transformation of RCC data into RICC/RPD values with a high degree of accuracy and will facilitate comprehensive retrospective evaluation of test results.
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Authors
Yurika Fujita, Toshio Kasamatsu, Naohiro Ikeda, Naohiro Nishiyama, Hiroshi Honda,