新华社华盛顿8月7日电（记者林小春）两项7日发表在美国《科学－转化医学》杂志上的研究称，马兜铃酸会导致人体发生大量基因突变，从而引发癌症，其致癌性强于烟草和紫外线。
马兜铃酸天然存在于马兜铃、寻骨风、天仙藤和朱砂莲等马兜铃科植物中。20多年前，含有这类成分的中草药减肥药被发现会导致肾损害，后来人们又发现它还增加罹患尿路癌症的风险。约10年前，世界卫生组织下属的国际癌症研究中心将马兜铃酸列为一类致癌物。
美国约翰斯·霍普金斯大学与纽约州立大学石溪分校等机构研究人员在一项研究中报告说，他们对接触过马兜铃酸的19名上尿路癌症患者以及没有接触这种毒物的另7名患者进行了全外显子组测序。结果发现，马兜铃酸接触组每名患者平均发生753个基因突变，而非马兜铃酸接触组每名患者只有91个基因突变。研究表明，马兜铃酸能引发的基因突变数量高于烟草和紫外线。
另一项研究由来自新加坡、美国与中国台湾等多个医学机构的研究人员合作完成。他们利用全基因组和外显子组测序技术证实，接触马兜铃酸可能会引起过去被认为由其他致癌因素导致的癌症。例如，一种过去被认为是由吸烟引起的上尿路癌症和一种过去被归因于某种慢性肝炎感染所致的肝癌，可能均与马兜铃酸有关。研究人员表示，这是首次证实马兜铃酸与肝癌之间的相关性。
2004年，中国国家食品药品监督管理局根据对含马兜铃酸药材及其制剂不良反应的报道以及毒副作用研究和结果的分析，决定加强对含马兜铃酸药材及其制剂的监督管理，凡是含有马兜铃酸的中药制剂一律严格按处方药管理。（生物谷Bioon.com）
生物谷推荐的英文摘要
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006200
Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing
Margaret L. Hoang1, Chung-Hsin Chen2, Viktoriya S. Sidorenko3, Jian He1, Kathleen G. Dickman3,4, Byeong Hwa Yun5, Masaaki Moriya3, Noushin Niknafs6, Christopher Douville6, Rachel Karchin6, Robert J. Turesky5, Yeong-Shiau Pu2, Bert Vogelstein1, Nickolas Papadopoulos1, Arthur P. Grollman3,4, Kenneth W. Kinzler1,* and Thomas A. Rosenquist3,*
In humans, exposure to aristolochic acid (AA) is associated with urothelial carcinoma of the upper urinary tract (UTUC). Exome sequencing of UTUCs from 19 individuals with documented exposure to AA revealed a remarkably large number of somatic mutations and an unusual mutational signature attributable to AA. Most of the mutations (72%) in these tumors were A:T-to-T:A transversions, located predominantly on the nontranscribed strand, with a strong preference for deoxyadenosine in a consensus sequence (T/CAG). This trinucleotide motif overlaps the canonical splice acceptor site, possibly accounting for the excess of splice site mutations observed in these tumors. The AA mutational fingerprint was found frequently in oncogenes and tumor suppressor genes in AA-associated UTUC. The AA mutational signature was observed in one patient’s tumor from a UTUC cohort without previous indication of AA exposure. Together, these results directly link an established environmental mutagen to cancer through genome-wide sequencing and highlight its power to reveal individual exposure to carcinogens.
