SD大鼠背景数据采集试验中自发性肿瘤的发生情况及分析

Occurrence and Analysis of Spontaneous Tumors in Sprague-Dawley Rat Background Data Acquisition Test

目的SD大鼠是较为重要的实验大鼠品种之一,通过对其自发性肿瘤的类型和发生率的观察及统计,为临床前药物安全性评价工作提供了SD大鼠自发性肿瘤参照数据,对于开展临床前药物安全性评价工作,特别是长期毒性试验、致癌性试验及生殖试验尤为重要。方法本中心背景数据采集实验,将260只SPF级SD大鼠按体质量随机分为8组(A、B、C、D、E、F、G组和H组),并对应不同时期进行计划剖检(2、4、8、13、26、52、78周和104周),终止动物饲养时间为104周。结果在试验过程中,A、B、C、D、E组动物未见肿瘤发生,F、G、H组动物紧急剖检及计划剖检动物时发现肿瘤。动物剖检首次发现肿瘤时间为实验第24周,紧急剖检动物(动物约为30周龄)。共94只大鼠出现肿瘤,其中雌性59只、雄性35只。共检出肿瘤185例,良性肿瘤约占81.1%,恶性肿瘤约占18.9%,以良性肿瘤居多。最常见良性肿瘤为垂体前叶细胞腺瘤、乳腺纤维腺瘤。恶性肿瘤以乳腺癌、垂体前叶细胞腺癌、白血病、副泪腺癌发生居多,同时发现垂体前叶细胞腺癌、组织细胞肉瘤、白血病、支气管腺癌、乳腺癌等恶性肿瘤出现了对周围及全身组织脏器的转移。除明显自发性肿瘤发生外,还可见动物不同组织脏器的不典型增生和肝细胞变异灶。结论根据本中心SD大鼠背景数据采集试验结果,提示SD大鼠在30周龄后自发性肿瘤发生机率提高。肿瘤易发部位为垂体、乳腺、皮肤及皮下组织。常见自发性肿瘤为垂体前叶细胞腺瘤、乳腺纤维腺瘤等。雌性动物较雄性动物肿瘤发生率高。同时与国内外各研究机构的结果比较有一定的差异,可能大鼠自发性肿瘤类型及发生率与大鼠自身差异及饲养环境等有密切的联系。

Objective Sprague-Dawley rat is one of the important species in rats.To supply the reference data of spontaneous tumors of Sprague-Dawley rat for the drug preclinical safety evaluation,the types of spontaneous tumors of Sprague-Dawley rat were observed and their incidence of statistics was analyzed.Above all,the data would be so important to the long-term toxicity test,the carcinogenic test and the reproductive toxicity test.Method In the background data of acquisition test,260 SD rats were randomly divide into eight groups(A group,B group,C group,D group,E group,F group,G group and H group)according to weight.The animals of the above groups were dissected respectively in the planning anatomy at 2 weeks,4 weeks,8 weeks,13 weeks,26 weeks,52 weeks,78 weeks and 104 weeks.Result During the test,no tumor was found in the first five groups,but the tumor of the other three groups appeared not only in the planning anatomy but also in the urgent anatomy.The tumor was firstly discovered at 24th week of the test(the age of the animal was 30 weeks)among the animal necropsy and was found in total of 94 rats among which had 59 female rats and 35 male rats.A total of 185 tumors were detected,of which 81.1%were benign tumors and 18.9%were malignant tumors.In the benign tumors,the breast fibroadenoma and the anterior pituitary adenoma were the most common.The major malignant tumors were as follows:breast cancer,pituitary cell adenocarcinoma,leukemia,deputy lachrymal cancer.Meanwhile,the malignant tumor such as pituitary cell adenocarcinoma,histiocytic sarcoma,leukemia,bronchial adenocarcinoma,breast cancer transferred to the surrounding or the whole visceral organ.In addition to the obvious spontaneous tumors,the atypical hyperplasia and altered hepatocyte foci were visible.Conclusion According to the result derived from the background data acquisition test of SD rats of our center,the occurrence probability of spontaneous tumors had increased after 30 weeks old and the sites of predilection for the tumor were pituitarium,breast,skin and subcutaneous tissue.Such as the pituitary adenoma,breast fibroadenoma are the most common spontaneous tumors.The occurrence rate of the tumors in females was higher than males.At the same time,compared with the result from the different research institutions at home and abroad,the data had some differences.The different occurrence rates of the spontaneous tumors were considered to have a tight correlation of the individual difference and the feeding conditions.