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: 6289959
• 负责人: JOSEPH 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/6289959
• 关键词: cancer prevention; dietary restriction; laboratory rat; longitudinal animal study; neoplasm /cancer epidemiology; nonhuman therapy evaluation; nutrition related tag; outcomes research

The goal of this project is to identify and evaluate factors that may influence tumor incidence in laboratory rodents. We continued to investigate the impact of body weight differences on tumor incidence. We found that food restricting dosed and control animals to achieve idealized body weights in both 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. We also investigated the association between the severity of chronic progressive nephropathy (CPN) and the incidence of adrenal pheochromocytoma in male F344 rats. In control animals the incidence of pheochromocytoma was consistently higher in those animals with the more severe CPN. However, this correlation was not consistently observed in dosed groups. For example, among 28 NTP studies reporting a chemically-related increased severity of CPN, only three had a significant increase in pheochromocytoma. On the other hand, 5/6 NTP studies with increased incidence of pheochromocytoma had some degree of increased CPN severity. We concluded that this association may be a factor in the interpretation of some NTP studies. - Variability; tumor incidence; rodent carcinogenicity bioassays; body weight; dietary restriction. nephropathy, adrenal pheochromocytoma

本项目的目标是确定和评估可能影响实验室啮齿动物肿瘤发病率的因素。我们继续研究体重差异对肿瘤发生率的影响。我们发现，如果对照组比给药组动物需要更多的食物限制，则限制给药组和对照组动物的食物以达到两组的理想体重可能会产生假阳性结果。我们还发现，如果给药组和对照组的体重存在实质性差异，则给药组和对照组动物的相同食物限制可能会产生假阴性结果。我们还研究了慢性进展性肾病（CPN）的严重程度和雄性F344大鼠肾上腺嗜铬细胞瘤的发病率之间的关系。在对照动物中，具有更严重CPN的那些动物中嗜铬细胞瘤的发生率始终更高。然而，在给药组中并未始终观察到这种相关性。例如，在28项NTP研究中报告了化学相关的CPN严重程度增加，只有3项研究的嗜铬细胞瘤显著增加。另一方面，嗜铬细胞瘤发生率增加的5/6项NTP研究在一定程度上增加了CPN的严重程度。我们的结论是，这种关联可能是解释一些NTP研究的一个因素。- 变异性;肿瘤发生率;啮齿动物致癌性生物测定;体重;饮食限制。肾病，肾上腺嗜铬细胞瘤