Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.
Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.
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DOI：
10.3389/fgene.2014.00444
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发表时间：
2014
影响因子：
3.7
通讯作者：
Brindley PJ
中科院分区：
文献类型：
--
作者：
Correia da Costa JM;Vale N;Gouveia MJ;Botelho MC;Sripa B;Santos LL;Santos JH;Rinaldi G;Brindley PJ
在发展中国家，寄生虫感染仍然是一个长期存在的公共卫生问题。其中三种病原体，华支睾吸虫、华支睾吸虫和血吸虫血吸虫尤其令人担忧，因为它们被归类为第一类致癌物质：感染这些蠕虫是致癌的。采用液质联用(LC-MS/MS)方法，鉴定了类固醇激素类化合物(如氧化甾醇类、儿茶酚类雌激素类化合物等)。明显来自寄生虫的代谢物和相关的DNA加合物，在发育阶段，包括血吸虫的卵，在泌尿生殖系统血吸虫病患者的尿液中，以及在成虫阶段。由于这些甾醇衍生物被代谢成可修饰DNA的活性苯二酚，在其他情况下可导致乳腺癌和其他癌症，因此蠕虫寄生虫相关甾醇可能会在易患蠕虫寄生虫相关癌症的靶细胞中诱导肿瘤样表型，即在泌尿生殖系统血吸虫病情况下诱导膀胱尿路上皮细胞，在华支睾吸虫病情况下诱导胆管上皮细胞或胆管细胞。事实上，我们假设蠕虫诱导的癌症起源于寄生虫雌激素-宿主上皮细胞/尿路上皮细胞染色体DNA加合物，这里我们回顾了支持这一猜测的最新发现。
Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture.