Detection by 32P-postlabelling of 8-oxo-7,8-dihydro-2′-deoxyguanosine in DNA as biomarker of microcystin-LR- and nodularin-induced DNA damage in vitro in primary cultured rat hepatocytes and in vivo in rat liver
Detection by 32P-postlabelling of 8-oxo-7,8-dihydro-2′-deoxyguanosine in DNA as biomarker of microcystin-LR- and nodularin-induced DNA damage in vitro in primary cultured rat hepatocytes and in vivo in rat liver
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DOI：
10.1016/j.mrgentox.2004.06.010
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发表时间：
2004-11-14
影响因子：
1.9
通讯作者：
Périn, F
中科院分区：
文献类型：
--
作者：
Maatouk, I;Bouaïcha, N;Périn, F
微囊藻毒素- lr （MCYST-LR）和结节素（NOD）是由蓝藻产生的强效和特异性肝毒素。诱导自由基形成，降低谷胱甘肽水平和诱导DNA损伤是在这些肝毒素处理的大鼠肝细胞中发现的三个主要事件。然而，MCYST-LR-和nod介导的诱导DNA氧化损伤的机制尚未完全阐明。本研究的目的是确定MCYST-LR和NOD是否在体外和体内增加大鼠肝细胞中8-氧-7,8-二氢-2'-脱氧鸟苷（8-氧- dg）等DNA氧化损伤标志物的形成。大鼠肝细胞以低剂量（2和10 ng/ml）暴露于MCYST-LR或NOD，没有证据表明在形态学上有明显的细胞毒性作用，以及诱导8-oxo-dG的剂量和时间依赖性形成。此外，MCYST- lr处理大鼠（50杯/kg， ip）导致肝脏DNA中8-oxo-dG在处理后24小时显著增加，48小时下降。然而，nod诱导的DNA损伤在24和48小时均增加，与MCYST- lr诱导的效果相反。对这一氧化性DNA损伤标记物的影响表明，MCYST-LR和NOD确实会引起氧化应激，这可能至少部分地导致长期接触它们的肝脏毒性和致癌性。(C) 2004 Elsevier B.V.版权所有
Microcystin-LR (MCYST-LR) and nodularin (NOD) produced by cyanobacteria are potent and specific hepatotoxins. The induction of free-radical formation, reduction of glutathione levels and induction of DNA damage are three major events found in rat hepatocytes treated with these hepatotoxins. However, the mechanism of MCYST-LR- and NOD-mediated induction of oxidative DNA damage has not been fully elucidated. The objective of this study was to determine whether MCYST-LR and NOD increase the formation of a DNA oxidative damage marker such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in vitro in primary rat hepatocytes and in vivo in rat liver cells. Rat hepatocytes were exposed to MCYST-LR or NOD at low doses (2 and 10 ng/ml), at which there is no evidence of morphologically apparent cytotoxic effects, as well as an induced dose-and time-dependent formation of 8-oxo-dG. Moreover, MCYST-LR treatment of rats (50 mug/kg, ip) resulted in a significant increase of 8-oxo-dG in liver DNA, at 24 h after treatment before decreasing at 48 h. However, NOD-induced DNA damage was increased both at 24 and 48 h, in contrast to the MCYST LR-induced effect. The effects on this oxidative DNA damage marker indicates that MCYST-LR and NOD do evoke oxidative stress, which may contribute, at least in part, to their liver toxicity and carcinogenicity during long-term exposure. (C) 2004 Elsevier B.V. All rights reserved.