SOURCES OF VARIABILITY IN TUMOR INCIDENCE IN LONG TERM RODENT STUDIES

长期啮齿动物研究中肿瘤发生率变异的来源

• 批准号: 6162187
• 负责人: J K HASEMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162187
• 关键词: cancer prevention; dietary restriction; laboratory rat; longitudinal animal study; neoplasm /cancer epidemiology; nonhuman therapy evaluation; nutrition related tag; outcomes research

Summary of Work: An evaluation of data from the NTP Dietary Restriction Study indicates that food restricted animals show a significant reduction in a number of site-specific tumors relative to equivalently-sized ad libitum fed animals. These results suggest that a dietary restriction strategy that focuses on achieving similar body weights in dosed and control groups may produce false positive outcomes if substantially more food restriction is required for control groups than for dosed animals. We also found that equal food restriction to dosed and control animals may produce false negative outcomes if the resulting body weights are substantially different in dosed and control groups. An evaluation of correlations between the occurrence of site-specific tumors revealed little meaningful associations except for a strong negative correlation between the incidences of pituitary gland and testis tumors in male F344 rats. Mechanistic arguments were given to explain how differences in caging protocols may have been responsible for this observed negative correlation in tumor response. We evaluated the frequency of chemically- related decreases in tumor incidence in NTP studies. Many of these decreases are associated with the reduced body weights frequently observed in the dosed groups. The chemically-related decreased incidences of leukemia in rats appear to be related to spleen damage, i.e., chemically-related splenic toxicity is evident for most chemicals showing decreased incidences of leukemia. We concluded that most chemically-related tumor decreases observed in NTP studies are due to either random variability, associations with body weight, or (in the case of leukemia) splenic toxicity.

工作总结：对NTP饮食限制数据的评估 研究表明，食物限制动物显示出显着减少 在一些部位特异性肿瘤中， 自由采食动物。 这些结果表明， 策略，重点是在给药和 对照组可能会产生假阳性结果， 与给药动物相比，对照组需要限制食物。 我们还发现，给药组和对照组动物的食物限制相等， 如果产生的体重 在给药组和对照组中存在显著差异。 评价 部位特异性肿瘤的发生之间的相关性揭示了 除了强负相关外，几乎没有什么有意义的关联 雄性F344中垂体和睾丸肿瘤的发生率之间 大鼠机械论的论点被用来解释 笼养方案可能是造成这种观察到的阴性结果的原因 肿瘤反应的相关性。 我们评估了化学- NTP研究中肿瘤发生率的相关降低。 这些减少中的许多与体重减轻有关 在给药组中经常观察到。 化学相关 大鼠白血病发病率的降低似乎与脾有关 损害，即，化学相关的脾毒性对于大多数 白血病发病率下降的化学物质。 我们的结论是 NTP研究中观察到的大多数化学相关肿瘤减少是由于 随机变异性，与体重的关联，或（在 例白血病）脾毒性。