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呋喃唑酮及其代谢物对两种鱼类致癌作用的评估。

Evaluation of the carcinogenic effects of furazolidone and its metabolites in two fish species.

作者信息

Auro A, Sumano H, Ocampo L, Barragán A

机构信息

Departamento de Especies productivas no tradicionales, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México (UNAM), México City, México.

出版信息

Pharmacogenomics J. 2004;4(1):24-8. doi: 10.1038/sj.tpj.6500216.

DOI:10.1038/sj.tpj.6500216
PMID:14647403
Abstract

The major metabolite from the use of furazolidone (FZD) in mammals, birds and fish is 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1alpha, 2-di(2-oxo-oxazolidin-3-yl)iminomethyl-furo[2,3-beta]furan, also called 3-amine-2-oxazolidone (AOZ). A minor metabolite was identified as N-(5-amine-2-furfuryliden)-3-amine-2-oxazolidone (FOZ). To assess the potential carcinogenicity of FZD and the metabolic mixture of AOZ/FOZ, 11 mg FZD/kg feed/day was fed for 12 weeks to mollies (Poecilia formosa), an ornamental fish species prone to develop tumors. The rate of tumors was quantified and defined both in mollies and their offspring. Then, some fish was made into fishmeal and incorporated into fish food at 500 g of meal/kg of food and fed to other mollies for 12 weeks. The rate of tumors was assessed. A similar trial design was carried out in tilapia fish (Oreochromis niloticus) by adding 50 mg FZD/kg to the feed for 90 days. All animals were placed in glass fishponds under controlled laboratory conditions. Each week, a significant biomass was collected from both groups to assess the macroscopic and histopathological changes. All mollies developed melanohistiocytomic tumors in the liver and other organs. Offspring from surviving mollie females stimulated to breed showed no changes compared to control animals. None of the mollies fed with the mollie-meal food contaminated with AOZ/FOZ developed tumors. Neither tilapia medicated with FZD nor tilapia fed with tilapia-meal contaminated with AOZ/FOZ developed tumors. These results do not support the established viewpoint that FZD must be banned from trophic chains based on its potential carcinogenic properties.

摘要

呋喃唑酮(FZD)在哺乳动物、鸟类和鱼类体内的主要代谢产物是2,3 - 二氢 - 3 - 氰甲基 - 2 - 羟基 - 5 - 硝基 - 1α, 2 - 二(2 - 氧代 - 恶唑烷 - 3 - 基)亚氨基甲基 - 呋喃并[2,3 - β]呋喃,也称为3 - 氨基 - 2 - 恶唑烷酮(AOZ)。一种次要代谢产物被鉴定为N - (5 - 氨基 - 2 - 糠叉基)- 3 - 氨基 - 2 - 恶唑烷酮(FOZ)。为评估FZD以及AOZ/FOZ代谢混合物的潜在致癌性,以11毫克FZD/千克饲料/天的剂量给摩利鱼(帆鳉,Poecilia formosa)喂食12周,摩利鱼是一种易于发生肿瘤的观赏鱼品种。对摩利鱼及其后代的肿瘤发生率进行了量化和界定。然后,将一些鱼制成鱼粉,并以500克鱼粉/千克食物的比例添加到鱼食中,再喂给其他摩利鱼12周。评估肿瘤发生率。通过在饲料中添加50毫克FZD/千克,对罗非鱼(尼罗罗非鱼,Oreochromis niloticus)进行了为期90天的类似试验设计。所有动物都被置于实验室控制条件下的玻璃鱼塘中。每周从两组中收集大量样本,以评估宏观和组织病理学变化。所有摩利鱼在肝脏和其他器官中都出现了黑素组织细胞瘤。存活的摩利鱼雌性繁殖的后代与对照动物相比没有变化。喂食被AOZ/FOZ污染的摩利鱼鱼粉食物的摩利鱼均未发生肿瘤。用FZD药浴的罗非鱼以及喂食被AOZ/FOZ污染的罗非鱼鱼粉的罗非鱼均未发生肿瘤。这些结果不支持基于其潜在致癌特性而必须在食物链中禁用FZD这一既定观点。

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