King-Herbert Angela, Thayer Kristina
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Toxicol Pathol. 2006;34(6):802-5. doi: 10.1080/01926230600935938.
The National Toxicology Program (NTP) hosted a workshop, "Animal Models for the NTP Rodent Cancer Bioassay: Strains and Stocks--Should We Switch?" on June 16-17, 2005, at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. The workshop's objectives were to determine (1) whether the currently used models, the F344/N rat and B6C3F1/N mouse, continue to be appropriate to identify substances that may pose a carcinogenic hazard for humans and (2) whether the NTP should consider conducting cancer bioassays using multiple strains of rats and/or mice to better capture the range of genetic variability. Workshop participants advised the NTP to discontinue using the current F344/N strain due to the recent issues with fertility, seizure activity, and chylothorax and provided several options on how the program should approach identifying and selecting a new rat model. Participants believed that the B6C3F1/N mouse is still appropriate for use by the NTP, but suggested the NTP take steps to better understand and address increases in background rates of liver tumors in this strain. Finally, the participants supported the NTP exploring the use of the multiple strain approach, although they raised many questions concerning data interpretation and feasibility. This article also outlines the NTP's next steps in pursuing the workshop recommendations.
2005年6月16日至17日,美国国家毒理学计划(NTP)在北卡罗来纳州三角研究园的国家环境健康科学研究所(NIEHS)举办了一场题为“NTP啮齿动物癌症生物测定的动物模型:品系与种群——我们应该更换吗?”的研讨会。该研讨会的目标是确定:(1)目前使用的模型,即F344/N大鼠和B6C3F1/N小鼠,是否仍然适合识别可能对人类构成致癌风险的物质;(2)NTP是否应考虑使用多种品系的大鼠和/或小鼠进行癌症生物测定,以更好地涵盖遗传变异性范围。研讨会参与者建议NTP停止使用当前的F344/N品系,因为该品系近期出现了生育、癫痫活动和乳糜胸等问题,并就该计划应如何识别和选择新的大鼠模型提供了几种选择。参与者认为B6C3F1/N小鼠仍适合NTP使用,但建议NTP采取措施,更好地了解和解决该品系肝脏肿瘤背景发生率上升的问题。最后,参与者支持NTP探索使用多种品系的方法,尽管他们对数据解释和可行性提出了许多问题。本文还概述了NTP在落实研讨会建议方面的下一步计划。