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评估新生小鼠和新生仓鼠对致癌DNA的敏感性
Li Sheng-Fowler1, Wei Tu1, Kathryn Phy1
1Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
概括
这项研究发现,目前的体内模型没有足够的灵敏度来检测疫苗中的瘤性DNA. 研究人员对新生小鼠和仓鼠进行了测试,但两种动物模型都无法从细胞系中可靠地检测导致瘤的DNA.
科学领域:
- 生物技术是生物技术.
- 在瘤学瘤学.
- 疫苗开发 疫苗开发
背景情况:
- 疫苗越来越多地使用致瘤细胞系制造,这引发了人们对细胞残留DNA的担忧.
- 评估这种残留DNA的致癌潜力对于疫苗安全至关重要.
研究的目的:
- 建立和评估体内测试,以量化来自瘤细胞系的DNA的致癌活性.
- 为了确定新生小鼠和仓鼠对通过瘤基因表达DNA诱导瘤的敏感性.
主要方法:
- 产生了三种瘤基因表达等离子体:pMSV-T24-H-ras (H-ras),pMSV-c-myc (c-myc) 和一个组合等离子体.
- 在小鼠中使用这些等离子体诱导瘤.
- 用不同剂量的联合等离子体和单基因等离子体对新生小鼠和老鼠进行注射,以评估瘤诱导和敏感性.
主要成果:
- 新生小鼠对瘤诱导的敏感性比新生仓鼠更高.
- 在这两种动物中,激活的H-ras瘤基因诱导了瘤,而单独的c-myc则没有.
- 来自诱导瘤的细胞系的DNA未能在新生小鼠中诱导瘤,这表明测试灵敏度不足.
结论:
- 现有的体内模型缺乏检测疫苗中残留细胞DNA致癌性的灵敏度.
- 需要进一步开发更敏感的测定方法,以确保针对瘤原生细胞系衍生DNA的疫苗安全.
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