Genotoxicity of phenacetin in the kidney and liver of Sprague-Dawley gpt delta transgenic rats in 26-week and 52-week repeated-dose studies

• Published in: Toxicology (Amsterdam) Vol. 324; pp. 10 - 17
• Main Authors: Kawamura, Yuji, Hayashi, Hiroyuki, Masumura, Kenichi, Numazawa, Satoshi, Nohmi, Takehiko
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 03.10.2014
• Subjects: Analgesics, Non-Narcotic - toxicity; Animals; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Emergency; Female; gpt assay; gpt delta transgenic rat; Hypoxanthine Phosphoribosyltransferase - genetics; Hypoxanthine Phosphoribosyltransferase - metabolism; Kidney - drug effects; Kidney - enzymology; Kidney - pathology; Kidney Neoplasms - chemically induced; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Liver - drug effects; Liver - enzymology; Liver - pathology; Male; Mutagenicity Tests; Phenacetin; Phenacetin - toxicity; Point Mutation - drug effects; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Renal tumor; Repeated-dose study; Risk Assessment; Spi–assay; Target organ; Time Factors; gpt assay; Target organ; mutant frequency; Cm; 6-thioguanine; ICH; Center for Drug Evaluation and Research; CDER; 6-TG; OECD; Repeated-dose study; International Conference on Harmonisation; Spi –assay; MF; chloramphenicol; Phenacetin; Organisation for Economic Co-operation and Development; gpt delta transgenic rat; Renal tumor; Spi–assay; Spi(–)assay
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2014.07.003

Highlights • Phenacetin induced mutations in kidney, the target organ for carcinogenesis. • Phenacetin also induced mutations in liver, a nontarget organ. • Combined action of genotoxicity and renal injury may account for phenacetin-induced cancer. • gpt delta rat assay reveals roles of genotoxic and non-genotoxic mechanisms of carcinogenesis.