MISC

2000年

O-6-(fluorobenzyl)guanine and chloroethylnitrosourea in xenografted rat brain tumor in vivo

ACTA ONCOLOGICA
  • M Takahashi
  • ,
  • K Mineura
  • ,
  • K Watanabe
  • ,
  • K Kohda

39
1
開始ページ
89
終了ページ
95
記述言語
英語
掲載種別
DOI
10.1080/028418600431030
出版者・発行元
SCANDINAVIAN UNIVERSITY PRESS

O-6-methylguanine-DNA methyltransferase (MGMT), one of the DNA repair enzymes; potently repairs DNA damage induced by chloroethylnitrosoureas (CENUs). Depletion of MGMT activity after treatment with MGMT inhibitors increases the sensitivity of tumor cells to CENUs. We tested the effect of O-6-(4-, 3- and 2-fluorobenzyl)guanines (4F, 3F and 2F, respectively), three newly synthesized MGMT inhibitors, on 1-(4-amino-2-methyl-5-pyrimidinyl)methy-3-(2-chloroethyl)-3-nitrosoureahydrochloride (ACNU) therapy in C6 tumor xenografts. Treatment with 4F + ACNU and 3F + ACNU significantly decreased tumor volume and extended the delay of growth in comparison to untreated mice (control group, p < 0.05). Both groups showed significantly lower proliferating indices than the control group (p < 0.05) 12 h after treatment. In contrast, 2F did not enhance the ACNU anti-tumor effect. These results indicate that O-6-(4- and 3-fluorobenzyl)guanines as well as O-6-benzylguanines enhance the effect of ACNU on the growth of C6 tumor xenografts in vivo.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1080/028418600431030
CiNii Articles
http://ci.nii.ac.jp/naid/10026995758
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/10752660
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000085950100014&DestApp=WOS_CPL