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BMC Genet.:培养细胞可替动物用于制药试验

关键词:BMC Genetics,培养细胞,制药

按照欧洲法律,和化妆品领域用动物做实验是受到限制的,但这些产品必须保证对人体的安全,为此一些大的公司不得不寻找替代性方法。据美国科学促进会网站近日报道,最近发表在网络期刊《生物医学中心:基因组学》(BMC Genomics)上的一篇论文提出了一种前卫的替代方法,用实验室培养的人类细胞替代动物实验。通过检测这些培养细胞的反应,就能区分出哪些化学品会造成过敏,并能预测过敏程度。

人们在日常的工作和生活中,每天都会接触到各种各样的化学制品,如机器油、洗涤剂、肥皂、各种日用化妆品等。而过度频繁地接触某种化学品,有可能导致过敏性皮炎、发痒和湿疹。除非找到造成过敏的化学药品源头,否则很难根治湿疹和其他过敏症状。

欧盟2009年发布的化妆品行业指导第7修正案规定,禁止在动物身上试验化妆品及其成分,这也意味着很难保证新开发的化妆品不会造成人体过敏。

瑞典伦德大学的研究人员利用全基因组特征检测了人类骨髓细胞系对已知化学药品的反应。根据检测结果,他们确定了200个基因的“生物标记特征”,能精确区分出会造成过敏的化学药品。将这些特征和已知的化学品性质相对照,就能预测该化学品是否造成过敏和过敏程度。

“根据化学制品登记、评估与批准管理规定,欧盟所有新出的和原有的化学制品都要经过安全测试,这一规定涵盖的化学品数量已经超过3万种,而且还在增加。”论文合著者卡尔·伯瑞贝克教授说,这要求有合适的方法来测试,“新替代方法中所用的细胞来自人体,尽管还处于初期阶段,但其效果更快也更好。它提供了一种通过识别低免疫原性的化学品来降低过敏风险的方法,确保消费者长期使用的化学制品是安全的”。( Bioon.com)

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A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

Henrik Johansson, Malin Lindstedt, Ann-Sofie Albrekt, Carl Borrebaeck

(provisional)Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This is commonly caused by immunological responses towards chemical haptens, subsequently leading to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusion sA gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.