Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang 524045, China; State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Ecotoxicol Environ Saf. 2022 Mar 1;232:113287. doi: 10.1016/j.ecoenv.2022.113287. Epub 2022 Feb 8.
6-benzylaminopurine (6-BA), classified as a "plant hormone", is an important ingredient in production of "toxic bean sprouts". Although there is no direct evidence of adverse effects, its hazardous effects have received some attention and aroused furious debate between proponents and environmental regulators. In this study, potential adverse effects of 6-BA were investigated by exposing zebrafish in vivo to 0.2 - 25 mg 6-BA/L. Results indicated that, when exposure was limited to early-life stage (4-36 hpf), 20 mg 6-BA/L caused early hatching, abnormal spontaneous movement, and precocious hyperactivity in zebrafish embryos/larvae. While under a continuous exposure regime, 6-BA at 0.2 mg/L was able to cause hyperactive locomotion and transcription of genes related to neurogenesis (gnrh3 and nestin) and endocrine systems (cyp19a and fshb) in 5 dpf larvae. Quantification by use of LC/MS indicated bioaccumulation of 6-BA in zebrafish increased when exposed to 0.2 or 20 mg 6-BA/L. These results suggested that 6-BA could accumulate in aquatic organisms and disrupt neuro-endocrine systems. Accordingly, exposure to 0.2 mg 6-BA/L increased production of estradiol (E2) and consequently E2/T ratio in zebrafish larvae, which directly indicated 6-BA is estrogenic. In silico simulations demonstrated potential for binding of 6-BA to estrogen receptor alpha (ERa) and cytochrome P450 aromatase (CYP19A). Therefore, induction of estrogenic effects, via potential interactions with hormone receptors or disturbance of downstream transcription signaling, was possible mechanism underlying the toxicity of 6-BA. Taken together, these findings demonstrate endocrine disrupting properties of 6-BA, which suggest concerns about risks posed to endocrine systems.
6-苄氨基嘌呤（6-BA），归类为“植物激素”，是“毒豆芽”生产的重要成分。虽然没有直接的不良影响证据，但它的有害影响已经引起了一些关注，并在支持者和环境监管机构之间引发了激烈的争论。在这项研究中，通过将斑马鱼体内暴露于 0.2-25mg 6-BA/L 来研究 6-BA 的潜在不良影响。结果表明，当暴露仅限于生命早期阶段（4-36 hpf）时，20mg 6-BA/L 会导致斑马鱼胚胎/幼鱼提前孵化、自发性运动异常和过度活跃。而在连续暴露的情况下，0.2mg/L 的 6-BA 能够引起 5dpf 幼鱼过度活跃的运动和与神经发生（gnrh3 和 nestin）和内分泌系统（cyp19a 和 fshb）相关基因的转录。通过使用 LC/MS 进行定量分析表明，当暴露于 0.2 或 20mg 6-BA/L 时，6-BA 在斑马鱼体内的生物积累增加。这些结果表明，6-BA 可以在水生生物体内积累并破坏神经内分泌系统。因此，暴露于 0.2mg/L 的 6-BA 增加了斑马鱼幼鱼中雌二醇（E2）的产生，进而增加了 E2/T 比值，这直接表明 6-BA 具有雌激素作用。计算机模拟表明，6-BA 有可能与雌激素受体 alpha（ERa）和细胞色素 P450 芳香化酶（CYP19A）结合。因此，通过与激素受体的潜在相互作用或干扰下游转录信号，诱导雌激素作用可能是 6-BA 毒性的潜在机制。综上所述，这些发现表明 6-BA 具有内分泌干扰特性，这表明对内分泌系统构成的风险存在担忧。
