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Purine analogues kill resting lymphocytes by p53‐dependent and ‐independent mechanisms
Author(s) -
Pettitt A. R.,
Clarke A. R.,
Cawley J. C.,
Griffiths S. D.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01448.x
Subject(s) - purine analogue , nucleoside , purine , deoxyadenosine , biology , cytotoxic t cell , deoxycoformycin , fludarabine , purine nucleoside phosphorylase , nucleoside analogue , immunology , adenosine , cancer research , adenosine deaminase , chemistry , biochemistry , genetics , enzyme , in vitro , chemotherapy , cyclophosphamide
To resolve the controversy concerning the role of p53 in the killing of resting lymphocytes by purine nucleoside analogues, we examined the cytotoxic effects of chlorodeoxyadenosine, fludarabine and deoxycoformycin (plus deoxyadenosine) on unstimulated spleen cells from p53‐knockout versus wild‐type mice. p53‐knockout cells were more resistant to all three nucleosides than were wild‐type cells. However, substantial killing still occurred in the absence of p53, indicating that purine analogues can kill resting lymphocytes by both p53‐dependent and ‐independent mechanisms. We suggest that these results are relevant to chronic lymphoid malignancies, and that characterization of the p53‐independent component of nucleoside action may indicate potential ways of overcoming therapeutic resistance.