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Adenosine deaminase gene amplification in deoxycoformycin-resistant mammalian cells
Authors:P Rowland  J Pfeilsticker  P A Hoffee
Affiliation:1. Laboratoire de Chimie Organique et Analytique, Institut Supérieur de l''Education et de la Formation Continue (Université El Manar), Bardo 2000, Tunisia;2. Laboratoire des Interfaces et Matériaux Avancés (LIMA), Faculté des Sciences de Monastir (Université de Monastir), Bd. de l''Environnement, Monastir 5019, Tunisia;1. Bio-organic Chemistry Laboratory, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada;2. Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada;3. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada;1. Department of Medicine, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon, 400-712, Republic of Korea;2. Department of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea;1. Biochemistry Program, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia;2. Bioinformatics Program, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia;3. Department of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia;4. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia;1. Thompson Rivers University, Department of Chemistry, Kamloops, BC V2C 0C8, Canada;2. Universidad Autónoma de Madrid, Departamento de Química, Cantoblanco, 28049 Madrid, Spain;1. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Yushan Road, Qingdao 266003, PR China;2. Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology Qingdao 266237, PR China;3. Center for Innovation Marine Drug Screening &Evaluation, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China
Abstract:Deoxycoformycin (dCF)-resistant mutants of rat hepatoma, mouse LMTK-, and Chinese hamster ovary (CHO) cells have been isolated and shown to overproduce adenosine deaminase (ADA). The overproduction of ADA was found to be due to ADA-gene amplification in rat and mouse cells but not in CHO cells. Deoxycoformycin-resistant rat hepatoma cells have large HSRs (homogeneously staining regions), mouse cells carry DMs (Double minutes), and CHO cells do not appear to have any gross chromosomal anomalies. When dCF-resistant rat hepatoma and mouse cells are selected by increasing the concentration of the inhibitor in small increments, there is a good correlation between the increase in ADA gene copy number and the increase in the level of expression of ADA, suggesting that all of the amplified genes are equally active in the expression of ADA.
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