Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain.
Toxicol Appl Pharmacol. 2018 May 15;347:70-78. doi: 10.1016/j.taap.2018.04.004. Epub 2018 Apr 7.
Disinfection by-products (DBPs) are compounds produced in the raw water disinfection processes. Although increased cancer incidence has been associated with exposure to this complex mixture, the carcinogenic potential of individual DBPs remains not well known; thus, further studies are required. Haloacetic acids (HAAs) constitute an important group among DBPs. In this study, we have assessed the in vitro carcinogenic potential of three HAAs namely chloro-, bromo-, and iodoacetic acids. Using a long-term (8 weeks) and sub-toxic doses exposure scenario, different in vitro transformation markers were evaluated using a human urothelial cell line (T24). Our results indicate that long-term exposure to low doses of HAAs did not reproduce the genotoxic effects observed in acute treatments, where oxidative DNA damage was induced. No changes in the transformation endpoints analyzed were observed, as implied by the absence of significant morphological, cell growth rate and anchorage-independent cell growth pattern modifications. Interestingly, HAA-long-term exposed cells developed resistance to oxidative stress damage, what would explain the observed differences between acute and long-term exposure conditions. Accordingly, data obtained under long-term exposure to sub-toxic doses of HAAs could be more accurate, in terms of risk assessment, than under acute exposure scenarios.
消毒副产物(DBPs)是在原水消毒过程中产生的化合物。尽管接触这种复杂混合物与癌症发病率增加有关,但个别 DBPs 的致癌潜力仍不清楚;因此,需要进一步研究。卤乙酸(HAAs)是 DBPs 中的一个重要组成部分。在这项研究中,我们评估了三种卤乙酸,即氯乙酸、溴乙酸和碘乙酸的体外致癌潜力。使用长期(8 周)和亚毒性剂量暴露方案,使用人尿路上皮细胞系(T24)评估了不同的体外转化标志物。我们的结果表明,长期低剂量暴露于 HAAs 不会重现急性处理中观察到的遗传毒性效应,即诱导氧化 DNA 损伤。分析的转化终点没有变化,这意味着没有明显的形态学、细胞生长速率和非锚定依赖性细胞生长模式改变。有趣的是,HAA 长期暴露的细胞对氧化应激损伤产生了抗性,这可以解释急性和长期暴露条件下观察到的差异。因此,与急性暴露情况相比,在亚毒性剂量的 HAAs 长期暴露下获得的数据在风险评估方面可能更准确。