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气候变化情景下异环磷酰胺和顺铂暴露对贻贝转录组响应的影响。

Effects of ifosfamide and cisplatin exposure combined with a climate change scenario on the transcriptome responses of the mussel Mytilus galloprovincialis.

机构信息

Centre for Environmental and Marine Studies (CESAM) and Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.

Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research, IDAEA-CSIC, C/ Jordi Girona 18, 08034 Barcelona, Spain.

出版信息

Sci Total Environ. 2023 Aug 10;885:163904. doi: 10.1016/j.scitotenv.2023.163904. Epub 2023 May 2.

Abstract

Coastal ecosystems are currently exposed to pollutants and climate change. Namely, the increasing consumption of antineoplastic drugs and their potential release to aquatic ecosystems are raising concerns. Nevertheless, information regarding the toxicity of these drugs towards non-target species is scarce, especially considering climate change scenarios. Ifosfamide (IF) and cisplatin (CDDP) are among the antineoplastics already detected in aquatic compartments and due to their mode of action (MoA) can negatively affect aquatic organisms. This study evaluates the transcription of 17 selected target genes related to the MoA of IF and CDDP in Mytilus galloprovincialis gills exposed to environmentally relevant and toxicological meaningful concentrations (IF - 10, 100, 500 ng/L; CDDP - 10, 100, 1000 ng/L), under an actual (17 °C) and predicted warming scenario (21 °C). Results showed an upregulation of the cyp4y1 gene when exposed to the highest concentrations of IF, regardless of the temperature. Both drugs upregulated genes related to DNA damage and apoptosis (p53, caspase 8 and gadd45), especially under warmer conditions. Increased temperature also downregulated genes related to stress and immune responses (krs and mydd88). Therefore, the present results showed a gene transcriptional response of mussels to increasing concentrations of antineoplastics and that warmer temperatures modulated those effects.

摘要

沿海生态系统目前正面临着污染物和气候变化的威胁。特别是,抗肿瘤药物的消费不断增加,以及它们有可能被释放到水生生态系统中,这引起了人们的关注。然而,关于这些药物对非目标物种的毒性的信息却很少,尤其是在考虑到气候变化情景的情况下。异环磷酰胺(IF)和顺铂(CDDP)是已在水生环境中检测到的抗肿瘤药物之一,由于它们的作用方式(MoA),可能会对水生生物产生负面影响。本研究评估了贻贝鳃中与 IF 和 CDDP 的 MoA 相关的 17 个选定靶基因的转录情况,这些贻贝暴露于环境相关且具有毒理学意义的浓度(IF-10、100、500ng/L;CDDP-10、100、1000ng/L)下,分别在实际温度(17°C)和预测升温情景(21°C)下。结果表明,无论温度如何,IF 最高浓度暴露时,cyp4y1 基因的表达上调。这两种药物都上调了与 DNA 损伤和细胞凋亡相关的基因(p53、caspase 8 和 gadd45),尤其是在较温暖的条件下。高温还下调了与应激和免疫反应相关的基因(krs 和 mydd88)。因此,本研究结果表明,贻贝对不断增加的抗肿瘤药物浓度表现出基因转录反应,而较高的温度则调节了这些影响。

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