Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas (ICB), Universidade Federal do Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil.
Laboratório de Cianobactérias e Ficotoxinas, Instituto de Oceanografia (IO), Universidade Federal do Rio Grande (FURG), Rio Grande, RS 96203-900, Brazil.
Ecotoxicol Environ Saf. 2018 Oct;161:729-734. doi: 10.1016/j.ecoenv.2018.06.007. Epub 2018 Jun 25.
Cyanobacterial blooms of Microcystis aeruginosa represent a significant risk to the environment and have become a worldwide concern. M. aeruginosa can produce the hepatotoxins microcystins (MCs) with potential for tumor promotion. The present study evaluated the time-dependent effects in the transcription of tumor-related genes in the zebrafish, Danio rerio, exposed to dilutions of a M. aeruginosa lysate containing 3.5 and 54.6 µg L MCs. We used a cultured M. aeruginosa strain, RST 9501, which contains mainly the variant [D-Leu] MC-LR and originated from the Patos Lagoon Estuary (RS, Brazil). The exposure caused short-term repression of tumor suppressor genes and long-term repression of proto-oncogenes. These responses were more evident for p53 that was repressed with exposure for 6, 24 and 96 h, and fosab and myca that were consistently repressed with exposure for 384 h, when fish were exposed to both M. aeruginosa lysate dilutions, compared to controls (p < 0.05). The suppressor genes, baxa and gadd45α, and the proto-oncogene, junba, were suppressed mainly at 96 h, where both dilutions of the lysate caused repression compared to controls (p < 0.05). The p53 gene was the only gene to be induced; this occurred in fish exposed to lysate containing 3.5 µg L for 384 h. This is the first study to show that M. aeruginosa containing an environmentally relevant concentration of [D-Leu] MC-LR could cause time-dependent repression of proto-oncogenes and tumor suppressor genes in fish. The results suggest that short-term repression of tumor suppressor genes could participate in the mechanism of tumor promotion caused by M. aeruginosa in fish.
铜绿微囊藻水华对环境构成重大威胁，已成为全球性关注的问题。铜绿微囊藻可产生具有潜在肿瘤促进作用的肝毒素微囊藻毒素（MCs）。本研究评估了暴露于含有 3.5 和 54.6 µg/L MCs 的铜绿微囊藻裂解物稀释液中的斑马鱼（Danio rerio）肿瘤相关基因转录的时间依赖性效应。我们使用了一种源自巴西帕托斯泻湖河口（RS）的培养铜绿微囊藻菌株 RST 9501，该菌株主要含有变体[D-Leu] MC-LR。暴露导致抑癌基因的短期抑制和原癌基因的长期抑制。与对照组相比，暴露于两种铜绿微囊藻裂解物稀释液的鱼在 6、24 和 96 h 时 p53 受到抑制，fosab 和 myca 持续受到抑制，在 384 h 时更为明显（p<0.05）。与对照组相比，在 96 h 时，抑制基因 baxa 和 gadd45α 以及原癌基因 junba 受到抑制，两种稀释液均导致抑制（p<0.05）。p53 基因是唯一被诱导的基因；这发生在暴露于含有 3.5 µg/L 的裂解物 384 h 的鱼中。这是第一项表明含有环境相关浓度[D-Leu] MC-LR 的铜绿微囊藻可导致鱼类原癌基因和抑癌基因的时间依赖性抑制的研究。结果表明，抑癌基因的短期抑制可能参与了铜绿微囊藻在鱼类中引起的肿瘤促进机制。
