Perfluorooctane sulfonate promotes doxycycline-induced liver tumor progression in male Kras^v12 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-KRAS^G12V), 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 kras^V12 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.