如今，水生物种面临着与药物消费相关的各种环境风险。更具体地说，癌症患者数量的增加伴随着抗肿瘤药物的消耗增加，例如异环磷酰胺（IF）和环磷酰胺（CP）。这些药物在水生生态系统中被发现，引起了人们对其影响的担忧，特别是对河口物种的影响，因为海水是大陆污水的最终接收者。同时，生物体可能受到预测的气候变化的威胁，例如盐度变化。考虑到这一点，本研究旨在研究 IF 和 CP 以及盐度变化的综合影响。为此，使用在不同盐度水平（20、30 和 40）下分别暴露于 IF 和 CP (500 ng/L) 28 天的双壳类贻贝进行转录组学、生化和组织病理学评估。 IF和CP上调代谢相关基因cyp3a1，CP还影响abcc基因，显示出最小的盐度影响，并强调了这些代谢途径在贻贝中的重要性。盐度变化影响与细胞凋亡和细胞周期生长相关的基因的转录，例如p53，以及有氧代谢（ETS）、抗氧化剂（CAT、SOD、GSH）和生物转化机制（GST 活性）。这些发现表明贻贝对渗透压具有较高的代谢适应性。在CP暴露和低盐度下，贻贝在消化腺小管中表现出LPO水平升高和组织病理学影响，揭示了对M. galloprovincialis的有害影响，并表明代谢减慢和抗氧化机制的激活有助于防止控制和高盐度下的细胞损伤。总体而言，结果强调了抗肿瘤药物生态毒理学风险评估的必要性，特别是在可预见的气候变化情景下。版权所有 © 2024。由 Elsevier Ltd 出版。

Nowadays, aquatic species face a variety of environmental risks associated with pharmaceutical consumption. More specifically, the increased number of cancer patients has been accompanied by an increased consumption of antineoplastic drugs, such as ifosfamide (IF) and cyclophosphamide (CP). These drugs have been found in aquatic ecosystems, raising concerns about their impact, especially on estuarine species, as marine waters are the final recipients of continental effluents. Simultaneously, organisms may be threatened by predicted climatic changes, such as salinity shifts. Considering this, the present research intends to investigate the combined effects of IF and CP, and salinity shifts. For this, a transcriptomic, biochemical, and histopathological assessment was made using the bivalve species Mytilus galloprovincialis exposed for 28 days to IF and CP (500 ng/L), individually, at different salinity levels (20, 30, and 40). IF and CP up-regulated metabolism-related gene cyp3a1, with CP also affecting abcc gene, showing minimal salinity impact and highlighting the importance of these metabolic routes in mussels. Salinity shifts affected the transcription of genes related to apoptosis and cell cycle growth, such as p53, as well as the aerobic metabolism (ETS), the antioxidant (CAT, SOD, GSH) and biotransformation mechanisms (GST activity). These findings indicate mussels' high metabolic adaptability to osmotic stress. Under CP exposure and low salinity, mussels exhibited increased LPO levels and histopathological effects in digestive gland tubules, revealing detrimental effects towards M. galloprovincialis, and suggesting that a metabolic slowdown and activation of antioxidant mechanisms helped prevent cellular damage at control and high salinities. Overall, results reinforce the need for antineoplastics ecotoxicological risk assessment, especially under foreseen climate change scenarios.Copyright © 2024. Published by Elsevier Ltd.