Linear dose-response relationship of erythrocyte enzyme-activity mutations in offspring of ethylnitrosourea-treated mice |
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| Authors: | D J Charles W Pretsch |
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| Affiliation: | 1. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China;2. Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education and Beijing National Laboratory for Molecular Science (BNLMS), College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China;3. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;4. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China;5. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China;6. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing 100044, China;7. Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China;8. Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Beijing 100871, China;9. Center for Quantitative Biology, Peking University, Beijing 100871, China;10. Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518055, China;1. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA;2. Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA;3. Department of Neurology, Brain Tumor Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA;1. Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310058, China;2. Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing, China;3. Institute of Crop Science, Fujian Agricultural and Forest University, Fuzhou, 310058, China;1. Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;2. Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;3. Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;4. The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China;1. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;3. Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA;4. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;5. Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA;6. Instituto Nacional de Enfermedades Neoplásicas, 15038 Lima, Perú;7. Hospital Clínico Universitario, Biomedical Research Institute INCLIVA, Universidad de Valencia, 46010 Valencia, Spain |
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| Abstract: | The specific activity of 10 erythrocyte enzymes was measured to detect gene mutations in F1 offspring of male mice treated with 3 different doses of ethylnitrosourea (ENU). After administration of ENU or of the solvent (controls), the (101/El X C3H/El)F1 hybrid males were mated to untreated T-stock females. No enzyme-activity mutant was found in 3610 F1 offspring of the control group. After treatment of postspermatogonial germ-cell stages, 1 mutant in 1125 F1 offspring of males treated with 160 mg ENU/kg body weight, and 2 mutants in 1319 F1 offspring of a 250-mg/kg group were observed. After treatment of spermatogonia, 9 enzyme-activity mutants in 4247 F1 offspring of males treated with 80 mg ENU/kg body weight, 15 mutants in 3396 F1 offspring of a 160-mg/kg group, and 9 mutants in 1402 F1 offspring of a 250-mg/kg group were detected. The mutation frequencies in spermatogonia were significantly different from that of the controls (P less than 0.01). The dose-response curve was found to be linear. The frequencies of enzyme-activity mutations are comparable to those of recessive specific-locus mutations determined in the same experiments. Enzyme-activity mutants with reduced activity as well as mutants with enhanced activity were found. Genetic and biochemical characterization of enzyme-activity mutants was routinely performed. In inter se crossings of heterozygotes, no offspring expressing a third phenotype other than the wild type and the heterozygote were found in approximately half of the mutation studies. The recovered mouse mutants might be used as animal models to study corresponding genetic diseases in humans. |
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