Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin
Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin
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DOI：
10.1016/s0041-008x(03)00254-0
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发表时间：
2003-09-15
影响因子：
3.8
通讯作者：
Shih, SM
中科院分区：
文献类型：
--
作者：
Liu, BH;Yu, FY;Shih, SM
霉菌毒素是真菌的次生代谢产物，对人和动物的毒性作用非常多样。研究了棒曲霉毒素(PAT)和桔霉素(CTN)对中国仓鼠卵巢细胞(CHO-K1)、人外周血淋巴细胞和人胚胎肾细胞(HEK293)的遗传毒性和氧化损伤作用。PAT使CHO-K1和人淋巴细胞姐妹染色单体互换(SCE)频率显著增加，而CTN则无此作用。PAT还提高了经处理的CHO-K1的DNA缺口和断裂水平。在单细胞凝胶电泳法(SCGE)中，HEK293暴露于浓度大于15微米的PAT可诱导DNA链断裂；甲酰胺嘧啶-DNA糖基酶(FPG)处理后的尾矩值也显著增加。这表明在人类细胞中，PAT是一种强大的破碎剂，能够对DNA造成氧化损伤。然而，CTN处理的培养物的尾矩值没有明显变化，这表明CTN对HEK293没有遗传毒性。HEK293与CTN共同孵育后，热休克蛋白70(HSP70)的mRNA水平升高，但人8-羟基鸟嘌呤DNA糖基酶1(HOGG1)的mRNA水平无明显变化。PAT处理不影响HSP70和hOGGI基因的表达。(C)2003 Elsevier Inc.保留所有权利。
Mycotoxins are fungal secondary metabolites with very diversified toxic effects in humans and animals. In the present study, patulin (PAT) and citrinin (CTN), two prevalent mycotoxins, were evaluated for their genotoxic effects and oxidative damage to mammalian cells, including Chinese hamster ovary cells (CHO-K1), human peripheral blood lymphocytes, and human embryonic kidney cells (HEK293). PAT, but not CTN, caused a significant dose-dependent increase in sister chromatid exchange (SCE) frequency in both CHO-K1 and human lymphocytes. PAT also elevated the levels of DNA gap and break in treated CHO-K1. In the single cell gel electrophoresis (SCGE) assay, exposure of HEK293 to concentrations above 15 muM of PAT induced DNA strand breaks; the tail moment values also greatly increased after posttreatment with formamidopyrimidine-DNA glycosylase (Fpg). This suggests that in human cells PAT is a potent clastogen with the ability to cause oxidative damage to DNA. However, no significant change in the tail moment values in CTN-treated cultures was found, suggesting that CTN is not genotoxic to HEK293. Incubation of HEK293 with CTN increased the mRNA level of heat shock protein 70 (HSP70), but not that of human 8-hydroxyguanine DNA glycosylase 1 (hOGG1). PAT treatment did not modulate the expression of either HSP70 or hOGGI mRNA. (C) 2003 Elsevier Inc. All rights reserved.