按照歐洲法律,,制藥和化妝品領(lǐng)域用動物做實驗是受到限制的,,但這些產(chǎn)品必須保證對人體的安全,為此一些大的公司不得不尋找替代性方法,。據(jù)美國科學(xué)促進會網(wǎng)站近日報道,,最近發(fā)表在網(wǎng)絡(luò)期刊《生物醫(yī)學(xué)中心:基因組學(xué)》(BMC Genomics)上的一篇論文提出了一種前衛(wèi)的替代方法,用實驗室培養(yǎng)的人類細(xì)胞替代動物實驗,。通過檢測這些培養(yǎng)細(xì)胞的反應(yīng),,就能區(qū)分出哪些化學(xué)品會造成過敏,并能預(yù)測過敏程度,。
人們在日常的工作和生活中,,每天都會接觸到各種各樣的化學(xué)制品,,如機器油,、洗滌劑、肥皂,、各種日用化妝品等,。而過度頻繁地接觸某種化學(xué)品,有可能導(dǎo)致過敏性皮炎,、發(fā)癢和濕疹,。除非找到造成過敏的化學(xué)藥品源頭,否則很難根治濕疹和其他過敏癥狀,。
歐盟2009年發(fā)布的化妝品行業(yè)指導(dǎo)第7修正案規(guī)定,,禁止在動物身上試驗化妝品及其成分,這也意味著很難保證新開發(fā)的化妝品不會造成人體過敏,。
瑞典倫德大學(xué)的研究人員利用全基因組特征檢測了人類骨髓白血病細(xì)胞系對已知化學(xué)藥品的反應(yīng),。根據(jù)檢測結(jié)果,他們確定了200個基因的“生物標(biāo)記特征”,能精確區(qū)分出會造成過敏的化學(xué)藥品,。將這些特征和已知的化學(xué)品性質(zhì)相對照,,就能預(yù)測該化學(xué)品是否造成過敏和過敏程度。
“根據(jù)化學(xué)制品登記,、評估與批準(zhǔn)管理規(guī)定,,歐盟所有新出的和原有的化學(xué)制品都要經(jīng)過安全測試,這一規(guī)定涵蓋的化學(xué)品數(shù)量已經(jīng)超過3萬種,,而且還在增加,。”論文合著者卡爾·伯瑞貝克教授說,這要求有合適的方法來測試,,“新替代方法中所用的細(xì)胞來自人體,,盡管還處于初期階段,但其效果更快也更好,。它提供了一種通過識別低免疫原性的化學(xué)品來降低過敏風(fēng)險的方法,,確保消費者長期使用的化學(xué)制品是安全的”。(生物谷 Bioon.com)
doi:10.1186/1471-2164-12-399
PMC:
PMID:
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.