title: p53 codon 72 genotype affects apoptosis by cytosine arabinoside in blood leukocytes.
abstract: 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.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonafè
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbi
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.forename: Chiara
authors.initials: C
authors.lastname: Trapassi
authors.forename: Claudia
authors.initials: C
authors.lastname: Gemelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Storci
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D003062:Codon; D003561:Cytarabine / Q000494:pharmacology*; D005091:Exons; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003062:Codon; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine