Induction of topoisomerase I cleavage complexes by 1-β-d-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells

1-β-d-Arabinofuranosylcytosine (Ara-C) is a nucleoside analog commonly used in the treatment of leukemias. Ara-C inhibits DNA polymerases and can be incorporated into DNA. Its mechanism of cytotoxicity is not fully understood. Using oligonucleotides and purified human topoisomerase I (top1), we found a 4- to 6-fold enhancement of top1 cleavage complexes when ara-C was incorporated at the +1 position (immediately 3′) relative to a unique top1 cleavage site. This enhancement was primarily due to a reversible inhibition of top1-mediated DNA religation. Because ara-C incorporation is known to alter base stacking and sugar puckering at the misincorporation site and at the neighboring base pairs, the observed inhibition of religation at the ara-C site suggests the importance of the alignment of the 5′-hydroxyl end for religation with the phosphate group of the top1 phosphotyrosine bond. This study also demonstrates that ara-C treatment and DNA incorporation trap top1 cleavage complexes in human leukemia cells. Finally, we report that camptothecin-resistant mouse P388/CPT45 cells with no detectable top1 are crossresistant to ara-C, which suggests that top1 poisoning is a potential mechanism for ara-C cytotoxicity.

La Région Méditerranéenne en 2020 et son Rôle dans le Réseau Energétjgue Européen, Vol. I: Analyse de la demande d'energie dans les PSEM (Horizons 2000-2010-2020)= The Mediterranean region in 2020 and its Role in the European Energy Network, Vol. I: Analysis of the energy demand in the SEMC (Horizons 2000-2010-2020).

None.

Data base development of automobile and light truck maintenance. Volume I - text and appendixes A-D. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Test facility inventory for the U.S. Department of Transportation. Final report. Volume III of VI. D-I.

National Highway Safety Bureau, Washington, D.C.

Collections concerning the church or congregation of Protestant Separatists formed at Scrooby in north Nottinghamshire, in the time of King James I : the founders of New-Plymouth, the parent-colony of New-England /

"This volume is in one sense a second edition of a tract which was printed in 1849, entitled 'Collections concerning the early history of the founders of a New Plymouth, the first colonists of New England'"--Preliminary notice.

An account of the ceremonies observed in the coronations of the kings and queens of England : viz. King James II and his royal consort, King William III and Queen Mary, Queen Anne, King George I, and King George II and Queen Caroline.

In anticipation of the coronation of King George III.

Vospominanīi︠a︡ ob Īoanni︠e︡ d'Ark ei︠a︡ pazha i sekretari︠a︡ Lui de Konta. Izvlek iz drevnikh arkhivov Frant︠s︡īi i izdal Mark Tvėn. (Personal recollections of Ioan of Arc etc.)

Mode of access: Internet.

Births, marriages, and deaths returned from Hartford, Windsor, and Fairfield, and entered in the early land records of the colony of Connecticut : volumes I and II of land records and no. D of colonial deeds /

Includes bibliographical references and index.

The earliest English translation of the first three books of the De imitatione Christi, now first printed from a ms. in the library of Trinity college, Dublin, with various readings from a ms. in the University library, Cambridge. Also the earliest printed translation of the whole work from a copy in the British museum (Books I-III by William Atkynson, D. D., book IV by the Lady Margaret, mother of K. Henry VII, and countess of Richmond and Derby).

Mode of access: Internet.