Perfluorooctane sulfonate promotes doxycycline-induced liver tumor progression in male Krasv12 transgenic zebrafish.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that has been widely detected in the environment and has caused growing international concern. The liver is the main target organ of PFOS exposure. Animal experiments have shown that PFOS exposure can increase the risk of liver tumorigenesis. However, whether PFOS can accelerate liver tumor progression is still unclear. In this study, transgenic zebrafish Tg(fabp10:rtTA2s-M2; TRE2:EGFP-KRASG12V), a hepatocellular carcinoma (HCC) model that can cause liver tumorigenesis by doxycycline (DOX) induction, was used to investigate the effect of PFOS exposure in HCC progression. The male krasV12 transgenic zebrafish were exposed to 20 mg/L DOX, 500 µg/L PFOS or combined 20 mg/L DOX and 500 µg/L PFOS for 10 d. The results showed that co-treated with PFOS and DOX caused oncogenic Kras-induced liver enlargement, increased the percentages of zebrafish with HCC, and aggravated metabolic reprogramming of liver. To the best of our knowledge, this study for the first proved that PFOS could promote liver tumor progression. Decreased vitamin D level and increased fatty acid intake caused by PFOS might be responsible for the tumor-promoting effects. The results suggest that attention should be paid to the tumor-promoting effects of PFOS when assessing its environmental health risks, and these findings provide new insights into the toxicity of PFOS.

Environmentally relevant concentrations of the flame retardant tris(1,3-dichloro-2-propyl) phosphate change morphology of female zebrafish.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was considered as a re-emerging environmental pollutant, and accumulated evidences suggested that it was global distributed in various environmental media. However, effect of TDCIPP on fish morphology remained largely unknown. In this study, one-month old zebrafish (Danio rerio) were exposed to 0, 0.05, 0.5 or 5 µg/L TDCIPP for 120 days, and effects on fish morphology and expressions of genes included in the development of muscle and bone were examined. Using landmark-based geometric morphometrics, we found that environmentally relevant concentrations of TDCIPP altered morphology of female zebrafish. Furthermore, TDCIPP decreased the ratio of caudal fin area to whole body area and muscle density. These effects were possibly resulted from the alteration in the expression of genes included in the development of muscle (myf5 and myog) and bone (bmp2b and bmp4).

Time-dependent inhibitory effects of Tris(1, 3-dichloro-2-propyl) phosphate on growth and transcription of genes involved in the GH/IGF axis, but not the HPT axis, in female zebrafish.

Growth curves were used to determine sensitive exposure windows for evaluation of developmental toxicity of chemicals to zebrafish. Dose- and time-dependent effects on body mass, body length and expression of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis were examined after exposure to environmentally relevant concentrations of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP). Based on growth curves, zebrafish grew most rapidly between 60 and 90 days post fertilization (dpf). Exposure to environmentally relevant concentrations of TDCIPP significantly decreased body mass and body length and down-regulated expression of several genes involved in the GH/IGF axis of female zebrafish, but no such effects were observed in male zebrafish. Exposure to TDCIPP did not change concentrations of thyroid hormones or expression of genes along the HPT axis in female and male zebrafish. These results suggest that growth stages of zebrafish between 60 and 90 dpf might be most appropriate for evaluation of developmental toxicity of chemicals, and down-regulation of genes involved in the GH/IGF axis, but not the HPT axis, might be responsible for the observed growth inhibition in females exposed to TDCIPP.