analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine分析了吉西他滨的体外和体内抗逆转录病毒活动.pdfVIP

Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine 1 1,2 6 6 6 Christine L. Clouser , Colleen M. Holtz , Mary Mullett , Duane L. Crankshaw , Jacquie E. Briggs , Jay 3 5 1,3 1,2,3,4 Chauhan , Ilze Matise VanHoutan , Steven E. Patterson , Louis M. Mansky * 1 Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Department of Diagnostic Biological Sciences, MinnCResT Program, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Center for Drug Design, University of Minnesota, Minneapolis, Minnesota, United States of America, 4 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America, 5 Masonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, Minneapolis, Minnesota, United States of America, 6 Department of Food Science and Nutrition, VA Medical Center, Minneapolis, Minnesota, United States of America Abstract Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with L