Alternaria toxins: Altertoxin II is a much stronger mutagen and DNA strand breaking mycotoxin than alternariol and its methyl ether in cultured mammalian cells

Alternaria toxins: Altertoxin II is a much stronger mutagen and DNA strand breaking mycotoxin than alternariol and its methyl ether in cultured mammalian cells
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DOI:
10.1016/j.toxlet.2012.08.003
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发表时间:
2012-10-02
期刊:
影响因子:
3.5
通讯作者:
Metzler, Manfred
Metzler, Manfred
中科院分区:
医学3区
文献类型:
--
作者:
Fleck, Stefanie C.;Burkhardt, Britta;Metzler, Manfred

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链格孢菌毒素II(Altertoxin II,ATX II)是链格孢菌产生的几种真菌毒素之一。它具有一种二醌结构,在鼠伤寒艾姆斯沙门氏菌中具有高度致突变性,但其在哺乳动物细胞中的致突变性以前尚未研究过。在这里,我们报告说,ATX II是一种有效的诱变剂在培养的中国仓鼠V79细胞,诱导浓度依赖性增加的突变在次黄嘌呤鸟嘌呤磷酸核糖基转移酶基因位点的浓度类似于已建立的诱变剂4-喹啉-N-氧化物。因此,ATX II作为诱变剂的效力比常见链格孢属毒素交链孢酚(AOH)和交链孢酚甲醚(AME)高至少50倍。与AOH和AME相反,ATX II不影响V79细胞的细胞周期。ATX II还导致V79细胞中的DNA链断裂,其效力再次超过AOH和AME。ATX II的高致突变性和DNA链断裂活性提出了一个问题,即这种链格孢属毒素是否对公众健康构成风险,并保证对食品和饲料中ATX II和其他二萘嵌苯醌类真菌毒素的存在进行研究。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Altertoxin II (ATX II) is one of the several mycotoxins produced by Alternaria fungi. It has a perylene quinone structure and is highly mutagenic in Ames Salmonella typhimurium, but its mutagenicity in mammalian cells has not been studied before. Here we report that ATX II is a potent mutagen in cultured Chinese hamster V79 cells, inducing a concentration-dependent increase of mutations at the hypoxanthine guanine phosphoribosyltransferase gene locus at concentrations similar to that of the established mutagen 4-quinoline-N-oxide. Thus, ATX II is at least 50-times more potent as a mutagen than the common Alternaria toxins alternariol (AOH) and alternariol methyl ether (AME). In contrast to AOH and AME, ATX II does not affect the cell cycle of V79 cells. ATX II also causes DNA strand breaks in V79 cells, with a potency again exceeding that of AOH and AME. The high mutagenic and DNA strand breaking activity of ATX II raises the question of whether this Alternaria toxin poses a risk for public health, and warrants studies on the occurrence of ATX II and other perylene quinone-type mycotoxins in food and feed. (c) 2012 Elsevier Ireland Ltd. All rights reserved.