Promotion effect of liver tumor progression in male kras transgenic zebrafish induced by tris (1, 3-dichloro-2-propyl) phosphate

A previous study reported that exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) could promote the progression of hepatocellular carcinoma (HCC) in female HCC model zebrafish. Due to the existence of gender disparity in the development of HCC between females and males, whether the promotion effect of TDCIPP still exists in male HCC model zebrafish remains unclear. In this study, Tg(fabp10:rtTA2s-M2; TRE2:EGFP-kras(G12v)), referred as kras transgenic zebrafish which was shown to be an inducible liver tumor model, was applied as experimental model to assess the promotion potential of TDCIPP for HCC in males. In brief, kras males were exposed to 20 mg/L doxycycline (DOX), 0.3 mg/L TDCIPP and a binary mixture of 20 mg/L DOX with 0.3 mg/L TDCIPP, and after exposure liver size, histopathology and transcriptional profiles of liver from these treatments were examined. With the involvement of TDCIPP, the liver size was significantly increased and the lesion of hepatocyte became more aggressive. Furthermore, expressions of genes involved in DNA replication and inflammatory response were simultaneously up-regulated in the treatment of TDCIPP compared with the solvent control and in the treatment of the binary mixture of the two chemicals compared to the single DOX treatment. Overall, our results suggested that TDCIPP had promotion effect on the progression of liver tumor in kras males.