The influence of p53 status on the cytotoxicity of fluorinated pyrimidine L-nucleosides.

Abstract:

:Fluorinated nucleoside analogues are a major class of cancer chemotherapy agents, and include the drugs 5-fluorouracil (5FU) and 5-fluoro-2'-deoxyuridine (FdUrd). The aim of this study was to examine the cellular toxicity of two novel fluorinated pyrimidine L-nucleosides that are enantiomers of D-nucleosides and may be able to increase selectivity for cancer cells as a result of their unnatural L-configuration. Two fluorinated pyrimidine L-nucleosides were examined in this study, L110 ([β-L, β-D]-5-fluoro-2'-deoxyuridine) and L117 (β-L-deoxyuridine:β-D-5'-fluoro-2'-deoxyuridine). The cytotoxicity of these L-nucleoside was determined in primary mouse fibroblasts and was compared with 5FU and FdUrd. In addition, the influence of p53 status on cytotoxicity was investigated. These cytotoxicity assays were performed on a matched set of primary mouse fibroblasts that were either wild type or null for the p53 tumour suppressor gene. It was found that cells lacking functional p53 were over 7500 times more sensitive to the drugs L110, L117 and FdUrd than cells containing wild type p53.

journal_name

Chem Biol Interact

authors

Murray V,Taylor CB,Gero AM,Lutze-Mann LH

doi

10.1016/j.cbi.2015.08.010

subject

Has Abstract

pub_date

2015-10-05 00:00:00

pages

102-9

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(15)30038-7

journal_volume

240

pub_type

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