Tennekes Henk, Gembardt Christian, Dammann Martina, van Ravenzwaay Bennard
Experimental Toxicology Services (E.T.S.) Nederland B.V., Spittaalstraat 15, NL-7201 EA Zutphen, The Netherlands.
Regul Toxicol Pharmacol. 2004 Aug;40(1):18-27. doi: 10.1016/j.yrtph.2004.04.003.
Time-related changes in the incidences of spontaneous neoplasms in adrenals (medulla), mamma, liver, pituitary, and (endocrine) pancreas were assessed statistically in Wistar, Sprague-Dawley, and F344 rats employed by BASF, Germany and major European contract research organizations over the last 20 years. Negative trends (7 of 80 cases) were observed for pituitary pars distalis adenomas in Sprague-Dawley males and females, for pancreas islet cell adenomas in BASF Wistar males and females, for benign adrenal pheochromocytomas in Sprague-Dawley males, for malignant pheochromocytomas in F344 males, and for mammary gland fibroadenomas in BASF Wistar females. Positive trends (13 of 80 cases) were observed for benign pheochromocytomas, mammary gland adenocarcinomas, and pancreas islet cell carcinomas in HanWistar females, for malignant pheochromocytomas and islet cell carcinomas in BASF Wistar males, for benign pheochromocytomas and islet cell adenomas in F344 males, for mammary gland fibroadenomas in Sprague-Dawley females, and for benign hepatocellular tumors in HanWistar males and females, and in BASF Wistar and Sprague-Dawley females. In 60 of 80 cases there were no statistically significant trends. These results indicate that the majority of tumor types showed no time trends and that, in each rat strain, certain tumor types are susceptible to slight positive or negative time trends. Accordingly, the validity and use of historical control data should be based on an organ- and strain-specific statistical analysis of tumor incidence over time.
德国巴斯夫公司以及欧洲主要合同研究组织在过去20年中使用的Wistar、Sprague-Dawley和F344大鼠,对肾上腺(髓质)、乳腺、肝脏、垂体和(内分泌)胰腺自发性肿瘤发生率随时间的变化进行了统计评估。在Sprague-Dawley雄性和雌性大鼠中,垂体远侧部腺瘤、在巴斯夫Wistar雄性和雌性大鼠中胰腺胰岛细胞腺瘤、在Sprague-Dawley雄性大鼠中良性肾上腺嗜铬细胞瘤、在F344雄性大鼠中恶性嗜铬细胞瘤以及在巴斯夫Wistar雌性大鼠中乳腺纤维腺瘤观察到负趋势(80例中有7例)。在HanWistar雌性大鼠中良性嗜铬细胞瘤、乳腺腺癌和胰腺胰岛细胞癌、在巴斯夫Wistar雄性大鼠中恶性嗜铬细胞瘤和胰岛细胞癌、在F344雄性大鼠中良性嗜铬细胞瘤和胰岛细胞腺瘤、在Sprague-Dawley雌性大鼠中乳腺纤维腺瘤以及在HanWistar雄性和雌性大鼠以及巴斯夫Wistar和Sprague-Dawley雌性大鼠中良性肝细胞肿瘤观察到正趋势(80例中有13例)。80例中有60例没有统计学上的显著趋势。这些结果表明,大多数肿瘤类型没有时间趋势,并且在每个大鼠品系中,某些肿瘤类型易受轻微的正或负时间趋势影响。因此,历史对照数据的有效性和用途应基于对肿瘤发生率随时间的器官和品系特异性统计分析。