Ecological Engineering Institute, Ljubljanska 9, 2000 Maribor, Slovenia.
Department for Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia.
Water Res. 2014 Apr 1;52:168-77. doi: 10.1016/j.watres.2014.01.007. Epub 2014 Jan 14.
The residues of anti-neoplastic drugs are new and emerging pollutants in aquatic environments. This is not only because of their increasing use, but also because due to their mechanisms of action, they belong to a group of particularly dangerous compounds. However, information on their ecotoxicological properties is very limited. We tested the toxicities of four anti-neoplastic drugs with different mechanisms of action (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET], and imatinib mesylate [IM]), and some of their binary mixtures, against two phytoplankton species: the alga Pseudokirchneriella subcapitata, and the cyanobacterium Synechococcus leopoliensis. These four drugs showed different toxic potential, and the two species examined also showed differences in their susceptibilities towards the tested drugs and their mixtures. With P. subcapitata, the most toxic of these drugs was 5-FU (EC50, 0.13 mg/L), followed by CDDP (EC50, 1.52 mg/L), IM (EC50, 2.29 mg/L), and the least toxic, ET (EC50, 30.43 mg/L). With S. leopoliensis, the most toxic was CDDP (EC50, 0.67 mg/L), followed by 5-FU (EC50, 1.20 mg/L) and IM (EC50, 5.36 mg/L), while ET was not toxic up to 351 mg/L. The toxicities of the binary mixtures tested (5-FU + CDDP, 5-FU + IM, CDDP + ET) were predicted by the concepts of 'concentration addition' and 'independent action', and are compared to the experimentally determined toxicities. The measured toxicity of 5-FU + CDDP with P. subcapitata and S. leopoliensis was higher than that predicted, while the measured toxicity of CDDP + ET with both species was lower than that predicted. The measured toxicity of 5-FU + IM with P. subcapitata was higher, and with S. leopoliensis was lower, than that predicted. These data show that these mixtures can have compound-specific and species-specific synergistic or antagonistic effects, and they suggest that single compound toxicity data are not sufficient for the prediction of the aquatic toxicities of such anticancer drug mixtures.
抗恶性肿瘤药物残留是水生环境中的新型和新兴污染物。这不仅是因为它们的使用越来越多，还因为它们的作用机制使它们属于一组特别危险的化合物。然而，关于它们的生态毒理学特性的信息非常有限。我们测试了四种具有不同作用机制的抗恶性肿瘤药物（5-氟尿嘧啶[5-FU]、顺铂[CDDP]、依托泊苷[ET]和甲磺酸伊马替尼[IM]）及其一些二元混合物对两种浮游植物的毒性：藻类假鱼腥藻和蓝细菌聚球藻。这四种药物表现出不同的毒性潜力，并且所检查的两种物种对测试药物及其混合物的敏感性也存在差异。对于假鱼腥藻，这些药物中最毒的是 5-FU（EC50，0.13mg/L），其次是 CDDP（EC50，1.52mg/L）、IM（EC50，2.29mg/L），毒性最小的是 ET（EC50，30.43mg/L）。对于聚球藻，最毒的是 CDDP（EC50，0.67mg/L），其次是 5-FU（EC50，1.20mg/L）和 IM（EC50，5.36mg/L），而 ET 高达 351mg/L 时没有毒性。测试的二元混合物（5-FU+CDDP、5-FU+IM、CDDP+ET）的毒性通过“浓度加和”和“独立作用”的概念进行预测，并与实验确定的毒性进行比较。假鱼腥藻和聚球藻中 5-FU+CDDP 的实测毒性高于预测值，而两种物种中 CDDP+ET 的实测毒性低于预测值。假鱼腥藻中 5-FU+IM 的实测毒性较高，聚球藻中 5-FU+IM 的实测毒性较低。这些数据表明，这些混合物可能具有特定于混合物和特定于物种的协同或拮抗作用，并且它们表明单一化合物毒性数据不足以预测此类抗癌药物混合物的水生毒性。
