大象抗癌的潜在机制和人类对DNA损伤的比较细胞反应
Lisa M Abegglen1, Aleah F Caulin2, Ashley Chan1
1Departments of Pediatrics (Hematology/Oncology) and Oncological Sciences, University of Utah School of Medicine, Salt Lake City.
JAMA
|October 9, 2015
概括
大象表现出显著的抗癌能力, 与人类细胞相比, 大象细胞对DNA损伤的反应更强, 提供了癌症抑制的进化见解.
科学领域:
- 进化医学
- 比较瘤学
- 基因组学
背景情况:
- 进化医学提供了对人类生理和疾病的洞察, 包括癌症生物学.
- 尽管大象的体型和寿命长, 但它们对癌症有很强的抵抗力,
研究的目的:
- 发现大象的抗癌机制.
- 为了比较大象,健康的人类和Li-Fraumeni综合征 (LFS) 患者的DNA损伤的细胞反应.
主要方法:
- 分析了包括644头大象在内的36种哺乳动物的尸体解剖数据, 以评估癌症耐药性.
- 测序非洲和亚洲大象的基因组以确定与癌症相关的基因.
- 从大象,人类对照和LFS患者的外周血液淋巴细胞暴露于电离辐射和多克索鲁比辛,以比较DNA损伤反应和亡.
主要成果:
- 癌症死亡率与哺乳动物的体型或寿命无关;大象的癌症死亡率低于人类 (11% - 25%).
- 非洲大象拥有至少20个TP53基因拷贝,而人类只有2个.
- 与人类淋巴细胞相比,大象的淋巴细胞在DNA损伤后表现出显著更高的p53介导的亡率.
结论:
- 象的癌症发病率较低可能与它们多重的TP53基因拷贝有关.
- 在DNA损伤后大象细胞中增强的亡反应表明了强大的癌症抑制机制.
- 这些发现可能为癌症抑制研究的进化策略铺平道路.
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