ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Integration of in vivo genotoxicity and short-term carcinogenicity assays using F344 gpt delta transgenic rats: in vivo mutagenicity of 2,4-diaminotoluene and 2,6-diaminotoluene structural isomers.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 35 citations in OpenAlex.
- Increased mutagenicity in the liver of MutaMouse females following oral treatment with commercial-grade toluene diisocyanate.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- New homozygous gpt delta transgenic rat strain improves an efficiency of the in vivo mutagenicity assay.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- Weight of evidence approach using a TK gene mutation assay with human TK6 cells for follow-up of positive results in Ames tests: a collaborative study by MMS/JEMS.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- Transgenic rat models for mutagenesis and carcinogenesis.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2017Review
- Past, Present and Future Directions ofFood safety (Tokyo, Japan) · 2016Review
- Article
- Genomic integration of lambda EG10 transgene in gpt delta transgenic rodents.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2015Article
- Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity.Journal of toxicologic pathology · 2013Article
- Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1-Nitropropane in F344 Rats.Journal of toxicologic pathology · 2011Article
- New short term prediction method for chemical carcinogenicity by hepatic transcript profiling following 28-day toxicity tests in rats.Cancer informatics · 2011Article
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Authors and funding
12 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
An important trend in current toxicology is the replacement, reduction, and refinement of the use of experimental animals (the 3R principle). We propose a model in which in vivo genotoxicity and short-term carcinogenicity assays are integrated with F344 gpt delta transgenic rats. Using this model, the genotoxicity of chemicals can be identified in target organs using a shuttle vector lambda EG10 that carries reporter genes for mutations; short-term carcinogenicity is determined by the formation of glutathione S-transferase placenta form (GST-P) foci in the liver. To begin validating this system, we examined the genotoxicity and hepatotoxicity of structural isomers of 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT). Although both compounds are genotoxic in the Ames/Salmonella assay, only 2,4-DAT induces tumors in rat livers. Male F344 gpt delta rats were fed diet containing 2,4-DAT at doses of 125, 250, or 500 ppm for 13 weeks or 2,6-DAT at a dose of 500 ppm for the same period. The mutation frequencies of base substitutions, mainly at G:C base pairs, were significantly increased in the livers of 2,4-DAT-treated rats at all three doses. In contrast, virtually no induction of genotoxicity was identified in the kidneys of 2,4-DAT-treated rats or in the livers of 2,6-DAT-treated rats. GST-P-positive foci were detected in the livers of rats treated with 2,4-DAT at a dose of 500 ppm but not in those treated with 2,6-DAT. Integrated genotoxicity and short-term carcinogenicity assays may be useful for early identifying genotoxic and nongenotoxic carcinogens in a reduced number of experimental animals.
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