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使用口腔微核试验检测安非拉酮诱导人类的致突变性和维生素 C 的保护作用。

Use of buccal micronucleus assay to determine mutagenicity induced by amfepramone in humans and the protective effects of vitamin C.

机构信息

a Health Science Center , Region of Campanha University, URCAMP , Bagé , Rio Grande do Sul , Brazil.

出版信息

J Toxicol Environ Health A. 2013;76(19):1121-8. doi: 10.1080/15287394.2013.841533.

DOI:10.1080/15287394.2013.841533
PMID:24274153
Abstract

The abusive use of amfepramone in Brazilian population has grown in recent years. Few studies have been conducted on amphetamine with respect to DNA damage, and there have been no apparent investigations examining the influence of amfepramone on humans. The aim of this study was to determine the possible mutagenic actions of amfepramone on humans using the micronucleus (MN) assay with buccal cells and the effects of supplementation with vitamin C as a potential protective agent. The study included 108 females with 52 as control and 56 taking amfepramone at 120 mg/d for at least the whole previous month. All women were intentionally selected to be nonsmokers and nondrinkers. After 30 d of amfepramone women were given amfepramone plus vitamin C use at 1000 mg/d for another month. Results showed a marked increase in the number of MN in amfepramone users in both basal and differentiated cells, indicating a mutagenic action. After vitamin C supplementation, a significant decrease in the frequency of MN and apoptosis was observed. Evidence indicates that the main mechanism of action of amfepramone in inducing DNA damage occurs through formation of reactive oxygen species (ROS), intercalation and topoisomerase binding, attributed to the presence of an N-dialkyl group. In addition, data demonstrated that vitamin C effectively inhibited amfepramone-induced DNA damage.

摘要

近年来,巴西人口中安非拉酮的滥用现象有所增加。关于安非他命对 DNA 损伤的研究很少,也没有明显的研究来检测安非拉酮对人类的影响。本研究旨在通过口腔细胞微核(MN)试验,以及补充维生素 C 作为潜在保护剂,来确定安非拉酮对人体的可能诱变作用。该研究包括 108 名女性,其中 52 名为对照组,56 名为安非拉酮组,每天服用 120 毫克,至少在整个前一个月内持续服用。所有女性都被有意选择为不吸烟和不饮酒者。在安非拉酮使用 30 天后,女性开始每天服用 1000 毫克的安非拉酮加维生素 C,再服用一个月。结果显示,在基础细胞和分化细胞中,安非拉酮使用者的 MN 数量明显增加,表明存在诱变作用。补充维生素 C 后,MN 和细胞凋亡的频率显著降低。有证据表明,安非拉酮诱导 DNA 损伤的主要作用机制是通过形成活性氧(ROS)、嵌入和拓扑异构酶结合,这归因于存在 N-二烷基基团。此外,数据表明维生素 C 能有效抑制安非拉酮引起的 DNA 损伤。

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