Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746, South Korea.
Department of Marine Science, College of Natural Sciences, Incheon National University, Incheon 406-772, South Korea.
Aquat Toxicol. 2014 Jul;152:232-43. doi: 10.1016/j.aquatox.2014.04.008. Epub 2014 Apr 15.
Despite being a strong toxicant for aquatic ecosystems, the effect of benzo[a]pyrene (B[a]P) on whole cytochrome P450 (CYP) biotransformation mechanisms has not been deeply investigated in aquatic organisms. To understand the mode of action of B[a]P on CYP molecular responses in fish, we analyzed the full spectrum of cyp genes and the activities of enzymes that are involved in detoxification and antioxidant defense systems after exposure to different concentrations of B[a]P over different time courses in the marine medaka, Oryzias melastigma. Upon B[a]P exposure, we found significant downregulation of cyp genes associated with steroidogenesis with decreased concentrations of actual hormones including estradiol (E2) and testosterone (11-KT), indicating that B[a]P-treated groups were closely associated with the dysfunction of hormone synthesis in a dose-dependent manner. In addition, B[a]P exposure strongly influenced transcriptional levels of antioxidant-related genes and their enzyme activities. Based on these results, we suggest that B[a]P induced the CYPs-involved systematic biotransformation mechanism with oxidative stress in the juvenile marine medaka, resulting in changes of endogenous hormonal levels and transcriptional levels of several steroidogenic metabolism-related CYPs.
尽管苯并[a]芘（B[a]P）是一种对水生生态系统有很强毒性的物质，但它对水生生物中整个细胞色素 P450（CYP）生物转化机制的影响还没有得到深入研究。为了了解 B[a]P 对鱼类 CYP 分子反应的作用方式，我们分析了海洋稻鱼在暴露于不同浓度的 B[a]P 不同时间后，与类固醇生成相关的 Cyp 基因的全貌，以及参与解毒和抗氧化防御系统的酶的活性。在 B[a]P 暴露后，我们发现与类固醇生成相关的 Cyp 基因显著下调，实际激素包括雌二醇（E2）和睾酮（11-KT）的浓度降低，表明 B[a]P 处理组与激素合成的功能障碍密切相关，且呈剂量依赖性。此外，B[a]P 暴露强烈影响抗氧化相关基因的转录水平及其酶活性。基于这些结果，我们认为 B[a]P 诱导了幼体海洋稻鱼中涉及系统生物转化机制的 CYP 和氧化应激，导致内源性激素水平和几种类固醇生成代谢相关 CYP 的转录水平发生变化。
