Mutagenicity of o-anisidine to the bladder of lacI- transgenic B6C3F1 mice: absence of 14C or 32P bladder DNA adduction
| Autor: | P. A. Lefevre, Jay M. Short, Brenda J. Rogers, James M. Parry, Nigel J. Jones, Helen Tinwell, K. Burnette, B.W. GIickman, E.A. Martin, John Ashby, G.S. Provost |
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| Rok vydání: | 1994 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Ratón Urinary system Urinary Bladder o-Anisidine Mice Transgenic Pharmacology chemistry.chemical_compound DNA Adducts Mice Oral administration Medicine Animals Carbon Radioisotopes Mutation frequency Carcinogen Urinary bladder Aniline Compounds Dose-Response Relationship Drug business.industry Mutagenicity Tests General Medicine DNA medicine.anatomical_structure chemistry Liver Toxicity Mutation Carcinogens Female business Phosphorus Radioisotopes |
| Zdroj: | Carcinogenesis. 15(10) |
| ISSN: | 0143-3334 |
| Popis: | Earlier studies have established that the rodent bladder carcinogen o-anisidine (OA) gives negative results in all of the standard rodent genetic toxicity assays. In the present study, a single oral administration of the maximum tolerated dose level (750 mg/kg) of OA to B6C3F1 mice yielded negative results in 32P-post-labelling assays of bladder and liver DNA (24 h after dosing). Likewise, 14C-ring-labelled OA administered orally to B6C3F1 mice gave no evidence of DNA binding 6, 12 or 24 h later. Administration of OA (750 mg/kg) to transgenic lacI- mice (Big Blue) led to a small increase in mutation frequency (MF) in the bladder, but not in the liver. Increased MFs were observed in the bladder following 1, 3 or 10 daily doses with sampling times of 1 or 2 weeks after the final dose. However, statistical significance (P < 0.01) was only reached 2 weeks after either 3 or 10 daily administrations of OA. The positive control chemical (dimethylnitrosamine) gave a positive result (P < 0.01) in the liver, but not the bladder, 7 days after a single administration of 10 mg/kg. The possibility that OA is mutagenic and carcinogenic to the rodent bladder via formation of radical species is suggested. |
| Databáze: | OpenAIRE |
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