Hubei Provincial Engineering Laboratory for Pond Aquaculture, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
Department of Biological Sciences, National University of Singapore, 117543, Singapore.
Ecotoxicol Environ Saf. 2020 Mar 15;191:110220. doi: 10.1016/j.ecoenv.2020.110220. Epub 2020 Jan 25.
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), 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.
先前的研究报告指出，接触三（1,3-二氯-2-丙基）磷酸酯（TDCIPP）可能会促进雌性 HCC 斑马鱼模型中肝细胞癌（HCC）的进展。由于女性和男性 HCC 发展之间存在性别差异，TDCIPP 的促进作用是否仍然存在于雄性 HCC 斑马鱼模型中尚不清楚。在这项研究中，Tg(fabp10:rtTA2s-M2; TRE2:EGFP-kras)，即 kras 转基因斑马鱼，被用作实验模型，以评估 TDCIPP 对雄性 HCC 的促进潜力。简而言之，kras 雄性被暴露于 20mg/L 强力霉素（DOX）、0.3mg/L TDCIPP 和 20mg/L DOX 与 0.3mg/L TDCIPP 的二元混合物中，然后检查这些处理后肝脏大小、组织病理学和肝脏转录谱。在 TDCIPP 的参与下，肝脏大小显著增加，肝细胞病变变得更加侵袭性。此外，与溶剂对照相比，TDCIPP 处理组中涉及 DNA 复制和炎症反应的基因表达同时上调，与单独 DOX 处理相比，在两种化学物质的二元混合物处理中也是如此。总体而言，我们的结果表明，TDCIPP 对 kras 雄性肝脏肿瘤的进展具有促进作用。
