Document 0297
 DOCN  M9460297
 TI    Cellular pharmacology and biological activity of
       5-carboranyl-2'-deoxyuridine.
 DT    9408
 AU    Schinazi RF; Goudgaon NM; Fulcrand G; el Kattan Y; Lesnikowski Z; Ullas
       G; Moravek J; Liotta DC; Veterans Affairs Medical Center (Atlanta),
       Decatur, GA 30033.
 SO    Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1113-20. Unique
       Identifier : AIDSLINE MED/94230028
 AB    PURPOSE: The intracellular uptake and metabolism of
       5-carboranyl-2'-deoxyuridine was investigated in primary human
       lymphocytes and in a T lymphoblastoid cell line using unlabeled and
       tritium labeled compound. The cytotoxicity and antiviral activity of the
       compound and stability to enzyme degradation was determined. METHODS AND
       MATERIALS: A novel method for radiolabeling the 5-carboranyl moiety of
       pyrimidine nucleosides was developed. Cells were exposed to unlabeled
       and tritium labeled 5-carboranyl-2'-deoxyuridine and the intracellular
       uptake and egress of the compound determined by high pressure liquid
       chromatography. The viability and growth of normal and malignant cells,
       including human and rat gliomas, in the presence of the compound was
       determined. RESULTS: Substantial levels of
       5-carboranyl-2'-deoxyuridine-5'-monophosphate are formed intracellularly
       and this major metabolite can be detected in cells 48 h after removal of
       the parent compound from the medium. No significant phosphorylation to
       the 5'-diphosphate or triphosphate of 5-carboranyl-2'-deoxyuridine was
       detected. Furthermore, radiolabeled 5-carboranyl-2'-deoxyuridine was not
       incorporated into deoxyribonucleic acid. 5-carboranyl-2'-deoxyuridine
       was essentially nontoxic to human lymphocytes as well as human or rat
       glioma cells, and had no marked effect in human lymphocytes acutely
       infected with human immunodeficiency virus type 1. CONCLUSION: The
       results demonstrate for the first time that 5-carboranyl-2'-deoxyuridine
       is phosphorylated intracellularly and suggest that it should be
       considered for further studies as a potential sensitizer for boron
       neutron capture therapy.
 DE    Boron Compounds/CHEMICAL SYNTHESIS/*METABOLISM/PHARMACOLOGY  *Boron
       Neutron Capture Therapy  Cell Survival/DRUG EFFECTS  Cells, Cultured
       Deoxyuridine/*ANALOGS & DERIVATIVES/CHEMICAL SYNTHESIS/METABOLISM/
       PHARMACOLOGY  Human  Phosphorylation  Radiation-Sensitizing
       Agents/*METABOLISM  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).