Olden Kenneth, Vulimiri Suryanarayana V
Authors' Affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, District of Columbia
Authors' Affiliation: National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, District of Columbia.
Cancer Prev Res (Phila). 2014 Jul;7(7):648-52. doi: 10.1158/1940-6207.CAPR-14-0124. Epub 2014 Jun 16.
In the current issue, Johnson and colleagues present exciting results, using biomarkers involved in aflatoxin B1 (AFB1)-induced hepatocarcinogenesis, as an example of a conceptual framework to target mechanisms of action in developing chemopreventive agents. Their innovative approach offers considerable promise for a field that has long been neglected. Proof-of-principle was demonstrated using a synthetic triterpenoid (CDDO-Im), which activates Nrf2 signal transduction pathway, inhibits formation of AFB1-induced DNA adducts and neoplastic hepatic foci, and alters the expression of genes associated with aflatoxin-mediated toxicity.
在本期杂志中,约翰逊及其同事展示了令人振奋的研究成果,他们以参与黄曲霉毒素B1(AFB1)诱导肝癌发生过程的生物标志物为例,构建了一个概念框架,用于靶向开发化学预防剂的作用机制。他们的创新方法为这个长期被忽视的领域带来了巨大的希望。使用一种合成三萜类化合物(CDDO-Im)进行了原理验证,该化合物可激活Nrf2信号转导通路,抑制AFB1诱导的DNA加合物和肿瘤性肝病灶的形成,并改变与黄曲霉毒素介导的毒性相关基因的表达。