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Chen, Sheng; Dang, Yao; Gong, Zhiyuan; Letcher, Robert J.; Liu, Chunsheng
Environmental pollution (1987), December 2019, Volume: 255Journal Article
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been detected in various environmental media and has been implicated as a weak mutagen or carcinogen, but whether TDCIPP can promote the progression of liver tumor remains unclear. In this study, krasV12 genetically modified zebrafish, Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasG12V), a model system in which liver tumors can be induced by doxycycline (DOX), was used to evaluate the liver tumor promotion potential of TDCIPP. Briefly, krasV12 transgenic females were exposed to 0.3 mg/L TDCIPP, 20 mg/L DOX or a binary mixture of 0.3 mg/L TDCIPP with 20 mg/L DOX, and liver size, histopathology, and transcriptional profiles of liver were determined. Treatment with TDCIPP resulted in increased liver size and caused more aggressive hepatocellular carcinoma (HCC). Compared with the exposure to DOX, TDCIPP in the presence of DOX up-regulated the expression of genes relevant with salmonella infection and the toll-like receptor signaling pathway. These results implied an occurrence of inflammatory reaction, which was sustained by the increase in the amount of infiltrated neutrophils in the liver of Tg(lyz:DsRed2) transgenic zebrafish larvae whose neutrophils were labelled by red fluorescent protein under the lysozyme C promoter. Furthermore, compared with the binary exposure of DOX and TDCIPP, treatment with a ternary mixture of TDCIPP, DOX and inflammatory response inhibitor (ketoprofen) significantly decrease the liver size and the amounts of neutrophils in the livers of kras and lyz double transgenic zebrafish larvae. Collectively, our results suggested that TDCIPP could promote the liver tumor progression by induction of hepatic inflammatory responses. Display omitted •TDCIPP exposure increased liver size in larvae of inducible zebrafish model for liver tumor.•TDCIPP exposure increased liver size and HSI values in female inducible zebrafish model for liver tumor.•Development of HCC induced in female inducible zebrafish model was promoted by TDCIPP.•Hepatic inflammatory responses induced by TDCIPP were involved in the promotion effect of liver tumor. For the first time, we found that TDCIPP could cause liver tumor progression by induction of hepatic inflammatory responses.
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