P53 codon 72 genotype affects apoptosis by cytosine arabinoside in blood leukocytes
P53 codon 72 genotype affects apoptosis by cytosine arabinoside in blood leukocytes
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DOI：
10.1016/s0006-291x(02)02691-8
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发表时间：
2002-12-13
影响因子：
3.1
通讯作者：
Franceschi, C
中科院分区：
文献类型：
--
作者：
Bonafè, M;Salvioli, S;Franceschi, C
个体之间对体外细胞凋亡的易感性存在很大差异，这一事实在预测体内对凋亡剂（如化疗中使用的凋亡剂）的反应方面具有潜在意义。在这份报告中，我们解决的问题是否在p53基因座的自然变异（脯氨酸精氨酸取代密码子72）影响的能力，外周血单核细胞从健康受试者进行体外细胞凋亡的细胞毒性药物阿糖胞苷。我们发现，携带精氨酸/精氨酸基因型的受试者的细胞在体外发生凋亡的程度高于精氨酸/脯氨酸受试者。这一发现表明，p53基因的自然发生的遗传变异解释了体外化疗药物敏感性的个体间差异的一部分，从而导致作为体内化疗反应及其不良反应的合格预测标志物。(C)2002 Elsevier Science（美国）。All rights reserved.
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. (C) 2002 Elsevier Science (USA). All rights reserved.