title: Musk xylene induces malignant transformation of human liver cell line L02 via repressing the TGF-β signaling pathway.
abstract: Musk xylene (MX) is a widely used synthetic nitro musk. Although the persistence and bioaccumulation of the synthetic musks are of concern since the nineteenth century, knowledge concerning the toxicity and environmental risks, especially the carcinogenicity is still limited. In the present study, the normal human hepatic cell line L02 was used to investigate the long-term carcinogenicity of MX. L02 cells were exposed to MX with different concentrations (10, 100, and 1000 μg/L) for 24 h, then with conventional culture. After MX exposure for 24 h, some irregular fusiform, protuberances and multinucleated cells were observed. Indefinite cell proliferation, ability of anchorage-independent proliferation and increase of migration and invision were also observed in subsequent experiments, which suggested the positive effects of MX on cell malignant transformation in vitro. Moreover, the up-regulated protein expression of some oncogenes (C-myc and PCNA) in each time points furthermore supported this conclusion. Meanwhile, decreased protein expression level of TGF-β and the downstream proteins, SMAD4 coupled with P15 were observed in MX-treated cells. In addition, after culturing for 20 passages, the proportion of cells in the G0/G1 phase was decreased. These results demonstrated that the TGF-β signaling pathway regulated indefinite cell proliferation might be responsible for the oncogenesis of MX.
authors.affiliation: Institute of Electromagnetics and Acoustics and Department of Electronic Science, Xiamen University, Xiamen, 361005, China; Medical College, Xiamen University, Xiamen, 361005, China. Electronic address: zhangyouyucxf@163.com.
authors.forename: Youyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Fisheries College, Jimei University, Xiamen, 361021, China.
authors.forename: Lixing
authors.initials: L
authors.lastname: Huang
authors.affiliation: Medical College, Xiamen University, Xiamen, 361005, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Medical College, Xiamen University, Xiamen, 361005, China.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
mesh_terms: D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated; D006801:Humans; D008099:Liver / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D014992:Xylenes / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D005229:Fatty Acids, Monounsaturated; D016212:Transforming Growth Factor beta; D014992:Xylenes; C008563:musk; C031447:musk xylene
keywords: Carcinogenicity; Musk xylene; TGF-β