CALORIE RESTRICTION DELAYS SPONTANEOUS TUMORIGENESIS IN P53-KNOCKOUT TRANSGENIC MICE
CALORIE RESTRICTION DELAYS SPONTANEOUS TUMORIGENESIS IN P53-KNOCKOUT TRANSGENIC MICE
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DOI：
10.1073/pnas.91.15.7036
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
PHANG, JM
中科院分区：
文献类型：
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作者：
HURSTING, SD;PERKINS, SN;PHANG, JM
通过基因靶向敲除 p53 肿瘤抑制基因（在人类肿瘤中经常突变）的两个等位基因的转基因小鼠提供了潜在有用的肿瘤发生模型，因为这些小鼠迅速发展出自发性肿瘤。为了确定 p53 敲除小鼠的肿瘤发生是否对实验操作敏感，评估了热量限制（CR；啮齿动物肿瘤的有效抑制剂）对肿瘤发展的反应。对雄性 p53 基因敲除无效和野生型同窝小鼠（每个治疗组 28-30 只）的肿瘤发展进行了 48 周的监测，这些小鼠随意进食 (AL) 或限制为 AL 碳水化合物热量摄入的 60%。相对于 AL:p53 敲除小鼠（中位生存 = 16 周），CR:p53 敲除小鼠（中位生存 = 25 周）的肿瘤发病和随后的死亡率延迟 (P = 0.0002)。任一种饮食治疗的野生型同窝小鼠的肿瘤发展和死亡率
Transgenic mice with both alleles of the p53 tumor suppressor gene (frequently mutated in human tumors) knocked out by gene targeting provide a potentially useful tumorigenesis model because these mice rapidly develop spontaneous tumors. To determine whether tumorigenesis in p53-knockout mice is sensitive to experimental manipulation, tumor development in response to calorie restriction (CR; a potent inhibitor of rodent tumors) was evaluated. Tumor development was monitored for 48 weeks in male nullizygous p53-knockout and wild-type littermate mice (28-30 per treatment group) fed ad libitum (AL) or restricted to 60% of AL carbohydrate calorie intake. CR:p53-knockout mice (median survival = 25 weeks) experienced a delay in tumor onset and subsequent mortality (P = 0.0002) relative to AL:p53-knockout mice (median survival = 16 weeks). Tumor development and mortality in wildtype littermates on either diet treatment were