Alkaline elution of rat testicular DNA: Detection of DNA strand breaks after in vivo treatment with chemical mutagens |
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| Affiliation: | 1. Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Seville, Spain;2. Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Córdoba, Campus de Rabanales, Córdoba, Spain;3. Department of Anatomy and Comparative Pathology and Anatomy, University of Córdoba, Campus de Rabanales, Córdoba, Spain;1. Merck and Co., Inc., West Point, PA, USA;2. Current address:Novavax Inc., Gaithersburg, MD, USA;1. Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan 250021, China;2. Department of Nephrology, Heze Municipal Hospital, Heze, China;1. Genetic and Molecular Toxicology, Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA;2. Investigative Toxicology, Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA;3. Comparative and Molecular Pathology, Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA;4. Genotoxicology Laboratory, Biosafety Research Center, Shizuoka, Japan;5. Pathology Laboratory, Biosafety Research Center, Shizuoka, Japan;6. Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA;1. Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012 Sevilla, Spain;2. Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Córdoba, Campus de Rabanales, Córdoba, Spain;3. IRNAS-CSIC, Av. Reina Mercedes, 10, 41012, Seville, Spain;1. Key Laboratory of Gas Hydrate, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou 510640, PR China;2. Guangzhou Center for Gas Hydrate Research, Chinese Academy of Sciences, Guangzhou 510640, PR China;3. University of Chinese Academy of Sciences, Beijing 100083, PR China |
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| Abstract: | The alkaline elution technique was used to measure DNA strand breaks in rat testes after intraperitoneal injection of several chemicals known to cause heritable mutations in rodents. Methyl methanesulfonate (MMS), ethyl methanesulfonate, methylnitrosourea, and ethylnitrosourea all produced single strand breaks in rat testicular DNA. For both of these pairs of homologous alkylating agents the relative potency was methyl analog ethyl analog. Strand breaks produced by MMS appeared rapidly (within 2 h) in rat testicular DNA and were partially repaired within 24 h. Studies with low doses of MMS indicate that the assay has the sensitivity to detect DNA strand breaks in the testis after a dose of only 5 mg/kg. Variability in DNA elution profiles for individual control animals and for individual animals given identical doses of MMS was small. In contrast to the results with known mutagens, intraperitoneal injection of nonmutagens such as dimethyl sulfoxide, phenol, and Triton X-15, did not produce strand breaks in testicular DNA.These data indicate that this assay detects DNA strand breaks in the rat testis. The results of several heritable mutagens and nonmutagens are qualitatively predictive of mutagenic activity in the testis. |
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