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 In Vitro. 2017 Dec;45(Pt 1):72-80. doi: 10.1016/j.tiv.2017.08.013. Epub 2017 Aug 24.
Epidemiological data indicate that chronic exposure to water disinfection by-products (DBPs) may result in increased risk of cancer. However, the real carcinogenic potential of individual DBPs is not well known. In this study, we assessed the in vitro carcinogenic potential of trichloronitromethane (TCNM) and bromonitromethane (BNM), two halonitromethanes (HNMs) commonly found in DBPs' mixtures at comparably high concentrations. Human lung BEAS-2B cells were exposed for 8weeks to TCNM and BNM, and the acquisition of different in vitro cancer-like features was evaluated. The results indicate that long-term exposure to non-cytotoxic doses of TCNM and BNM did not cause carcinogenic transformation as indicated by the absence of morphological changes, no effects on cell growth, no changes in the level of matrix metalloproteinases (MMPs) secretion, and no increased anchorage-independent cell growth capacity. Furthermore, TCNM- and BNM-exposed BEAS-2B cells were unable to enhance tumour growth directly or by indirect influence of the surrounding stroma. Our results indicate that the carcinogenic effects of DBP mixtures cannot be attributed to the evaluated HNMs. This is the first study evaluating the cell transformation effects of TCNM and BNM under a long-term exposure scenario using suitable hallmarks of the cancer process.
流行病学数据表明，慢性暴露于水消毒副产物（DBPs）可能会增加癌症风险。然而，个别 DBPs 的实际致癌潜力尚不清楚。在这项研究中，我们评估了两种卤代硝基甲烷（HNMs）——三氯硝基甲烷（TCNM）和一溴硝基甲烷（BNM）在体外的致癌潜力。这两种 HNMs 通常以相当高的浓度存在于 DBP 混合物中。人类肺 BEAS-2B 细胞暴露于 TCNM 和 BNM 中 8 周，评估了不同体外类似癌症特征的获得情况。结果表明，长期接触非细胞毒性剂量的 TCNM 和 BNM 不会导致致癌转化，这表现为没有形态变化、对细胞生长没有影响、基质金属蛋白酶（MMPs）分泌水平没有变化，以及锚定独立细胞生长能力没有增加。此外，TCNM 和 BNM 暴露的 BEAS-2B 细胞既不能直接增强肿瘤生长，也不能通过周围基质的间接影响来增强肿瘤生长。我们的结果表明，DBP 混合物的致癌作用不能归因于评估的 HNMs。这是第一项使用癌症过程的适当标志物评估 TCNM 和 BNM 在长期暴露情况下的细胞转化效应的研究。
