Inhibition of Nucleotide Excision Repair by Fludarabine

機関リポジトリ 被引用文献3件 参考文献33件

書誌事項

タイトル別名
  • Inhibition of Nucleotide Excision Repair by Fludarabine in Normal Lymphocytes in vitro, Measured by the Alkaline Single Cell Cel Electrophoreis (Comet) Assay

この論文をさがす

説明

Alkylating agents or platinum analogues initiate several excision repair mechanisms, the processes of which include incision and excision of the damaged nucleotide, gap filling by DNA resynthesis, and rejoining by ligation. The previous study described that nucleotide excision repair permitted an incorporation of fludarabine nucleoside (F-ara-A) into the repair patch, thereby inhibiting the DNA resynthesis. In the present study, to clarify the repair kinetics in view of the inhibition by F-ara-A, normal lymphocytes were stimulated to undergo nucleotide excision repair by ultraviolet C (UV) in the presence or the absence of F-ara-A. The repair kinetics were determined as DNA single strand breaks resulting from the incision and the rejoining using the alkaline single cell gel electrophoresis (Comet) assay. DNA resynthesis was evaluated by the uptake of tritiated thymidine into DNA. The lymphocytes initiated the incision step maximally at 1 h, and completed the rejoining process within 4 h after UV exposure. UV also initiated the thymidine uptake, which increased time-dependently and reached the plateau at 4 h. A 2-h pre-incubation with F-ara-A inhibited the repair in a concentration-dependent manner, with the maximal inhibition by 5 M. This inhibitory effect was demonstrated by the reduction of the thymidine uptake and by the inhibition of the rejoining. A DNA polymerase inhibitor, aphidicolin, and a ribonucleotide reductase inhibitor, hydroxyurea, were not so inhibitory to the repair process as F-ara-A at equimolar concentrations. The present findings suggest that such a mechanistic interaction may be applicable for therapeutic strategy against cancer especially in the context of resistant cells with an increased repair capacity.

収録刊行物

被引用文献 (3)*注記

もっと見る

参考文献 (33)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ