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暴露于蕨菜的放牧成年牛膀胱病变的H-ras免疫组化表达及分子分析

H-ras immunohistochemical expression and molecular analysis of urinary bladder lesions in grazing adult cattle exposed to bracken fern.

作者信息

Sardon D, de la Fuente I, Calonge E, Perez-Alenza M D, Castaño M, Dunner S, Peña L

机构信息

Department of Animal Medicine, Surgery and Pathology, Veterinary Faculty, Complutense University, 28040 Madrid, Spain.

出版信息

J Comp Pathol. 2005 Feb-Apr;132(2-3):195-201. doi: 10.1016/j.jcpa.2004.09.011.

DOI:10.1016/j.jcpa.2004.09.011
PMID:15737346
Abstract

Chronic ingestion of bracken fern (Pteridium spp.) by cattle produces upper alimentary tract and urinary bladder tumours causing a syndrome called bovine enzootic haematuria (BEH). Previous studies demonstrated ptaquiloside-DNA adducts and mutations in the h-ras gene in ileal epithelial cells of bracken fern-fed calves. Systematic inspection of the bladder mucosa of grazing cattle (n=126) from bracken-fern areas was carried out in a slaughterhouse. Of the 126 slaughterhouse cattle, 46 showed macroscopical lesions of the bladder. These bladders, together with six others known to have BEH, were examined histopathologically and by H-ras immunohistochemistry. Thirteen affected bladders were also examined by H-ras molecular analysis to detect mutations. Macroscopical and histological study of urinary bladder lesions found at the slaughterhouse revealed chronic cystitis (34.1%) and tumours (2.4%). There was significantly increased immunohistochemical expression of H-ras (P<0.05) in chronic cystitis (H-ras=53.24%) and bladder tumours (H-ras=63.60%) as compared with normal urinary bladders (H-ras=4.32%). A silent mutation (D38D) was detected in one animal with a mixed bladder tumour. The prevalence of urinary bladder lesions (chronic cystitis and tumours) obtained at the slaughterhouse was higher than expected. This study demonstrates that close inspection of urinary bladders of adult grazing cows is necessary to prevent possible human exposure to bracken-fern carcinogens. The absence of mutations in the codons of h-ras studied did not exclude the presence of polymorphisms in other regions of the gene (promoter or regulation sequences) or in other genes (belonging or not to the ras family) that significantly affect the H-ras protein.

摘要

牛长期摄入蕨类植物(蕨属)会引发上消化道和膀胱肿瘤,导致一种名为牛地方性血尿症(BEH)的综合征。先前的研究表明,喂食蕨类植物的小牛回肠上皮细胞中存在ptaquiloside-DNA加合物以及h-ras基因突变。在一家屠宰场对来自蕨类植物生长地区的放牧牛(n = 126)的膀胱黏膜进行了系统检查。在这126头屠宰牛中,46头显示出膀胱的宏观病变。对这些膀胱以及另外6头已知患有BEH的膀胱进行了组织病理学检查和h-ras免疫组织化学检查。还对13个受影响的膀胱进行了h-ras分子分析以检测突变。对屠宰场发现的膀胱病变进行的宏观和组织学研究显示,慢性膀胱炎占34.1%,肿瘤占2.4%。与正常膀胱(h-ras = 4.32%)相比,慢性膀胱炎(h-ras = 53.24%)和膀胱肿瘤(h-ras = 63.60%)中h-ras的免疫组织化学表达显著增加(P < 0.05)。在一头患有混合性膀胱肿瘤的动物中检测到一个沉默突变(D38D)。屠宰场获得的膀胱病变(慢性膀胱炎和肿瘤)的患病率高于预期。这项研究表明,有必要对成年放牧奶牛的膀胱进行仔细检查,以防止人类可能接触蕨类植物致癌物。在所研究的h-ras密码子中未发现突变并不排除该基因其他区域(启动子或调控序列)或其他基因(属于或不属于ras家族)中存在多态性,而这些多态性会显著影响H-ras蛋白。

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