Salaberria Iurgi, Hansen Bjørn Henrik, Asensio Vega, Olsvik Pål A, Andersen Rolf A, Jenssen Bjørn Munro
Department of Zoology and Animal Cell Biology, University of the Basque Country, Bilbao, Spain.
Toxicol Appl Pharmacol. 2009 Jan 1;234(1):98-106. doi: 10.1016/j.taap.2008.09.023. Epub 2008 Oct 10.
The herbicide atrazine (ATZ) is one of the most widely used pesticides in the world and is now under scrutiny for its alleged capacity to disrupt the endocrine system. Exhibiting negligible interaction with the estrogen receptor (ER), ATZ's mode of action remains to be elucidated. ATZ may act as an inducer of the enzyme aromatase, which converts androgens to estrogens, although other mechanisms should also be taken into consideration such as impairment of hepatic metabolism. Therefore we administered juvenile rainbow trout (Oncorhynchus mykiss) a dose of either 2 or 200 microg ATZ/kg, or of carrier control phosphate buffered saline (PBS) and we measured plasma concentrations of testosterone (T), 17beta-estradiol (E2) and vitellogenin (Vtg) 6 days after exposure. Simultaneously we analyzed hepatic gene expression of cytochrome P450 (CYP) 1A and pi-class glutathione S-transferase (GST-P), and catalase (CAT) activity. Although sex steroid levels showed no significant alterations, we found a dose-dependent increase in Vtg and a concomitant decrease in CYP1A. There was no effect of ATZ on GST-P mRNA levels but GST-P was positively correlated with CYP1A. Also, CYP1A was negatively correlated with liver CAT and E2, and varied with T concentrations in a hormetic manner. The results showed that ATZ can alter hepatic metabolism, induce estrogenic effects and oxidative stress in vivo, and that these effects are linked.
除草剂阿特拉津（ATZ）是世界上使用最广泛的农药之一，目前因其所谓的干扰内分泌系统的能力而受到审查。由于与雌激素受体（ER）的相互作用微不足道，ATZ的作用模式仍有待阐明。ATZ可能作为芳香化酶的诱导剂，将雄激素转化为雌激素，不过也应考虑其他机制，如肝脏代谢受损。因此，我们给幼年虹鳟鱼（Oncorhynchus mykiss）分别投喂2或200微克ATZ/千克的剂量，或投喂载体对照磷酸盐缓冲盐水（PBS），并在暴露6天后测量血浆中睾酮（T）、17β-雌二醇（E2）和卵黄蛋白原（Vtg）的浓度。同时，我们分析了细胞色素P450（CYP）1A、π类谷胱甘肽S-转移酶（GST-P）的肝脏基因表达以及过氧化氢酶（CAT）的活性。虽然性类固醇水平没有显著变化，但我们发现Vtg呈剂量依赖性增加，同时CYP1A减少。ATZ对GST-P mRNA水平没有影响，但GST-P与CYP1A呈正相关。此外，CYP1A与肝脏CAT和E2呈负相关，并以一种 hormetic 方式随T浓度变化。结果表明，ATZ可以改变肝脏代谢，在体内诱导雌激素效应和氧化应激，并且这些效应是相互关联的。
