p53 codon 72 genotype affects apoptosis by cytosine arabinoside in blood leukocytes

A wide difference in the susceptibility to undergo in vitro apoptosis exists among individuals, and this fact has potential implications in predicting the in vivo response to apoptotic agents, such as those employed in chemotherapy. In this report, we addressed the question whether the natural varia...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-12, Vol.299 (4), p.539-541
Main Authors: Bonafè, Massimiliano, Salvioli, Stefano, Barbi, Cristiana, Mishto, Michele, Trapassi, Chiara, Gemelli, Claudia, Storci, Gianluca, Olivieri, Fabiola, Monti, Daniela, Franceschi, Claudio
Format: Article
Language:English
Subjects:
Adult
Analysis of Variance
Antimetabolites, Antineoplastic - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Codon
Cytarabine - pharmacology
Cytosine arabinoside
Exons
Genetic Variation
Genotype
Humans
Leukocytes - drug effects
Leukocytes - metabolism
p53 codon 72
Polymorphism
Tumor Suppressor Protein p53 - genetics
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Summary:A wide difference in the susceptibility to undergo in vitro apoptosis exists among individuals, and this fact has potential implications in predicting the in vivo response to apoptotic agents, such as those employed in chemotherapy. In this report, we addressed the question whether the natural variability at p53 locus (the proline–arginine substitution at codon 72) affects the capacity of peripheral-blood mononuclear cells from healthy subjects to undergo in vitro apoptosis in response to the cytotoxic drug cytosine arabinoside. We found that cells from subjects carrying the arginine/arginine genotype undergo in vitro apoptosis at a higher extent in comparison to those from arginine/proline subjects. This finding suggests that naturally occurring genetic variability at p53 gene explains part of the inter-individual difference in the in vitro susceptibility to a chemotherapeutic drug, thus resulting as an eligible predictor marker of in vivo response to chemotherapy and its adverse effects.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)02691-8