Rapid Analysis of Effects of Environmental Toxicants on Tumorigenesis and Inflammation Using a Transgenic Zebrafish Model for Liver Cancer

Liver cancer remains to be a major health concern in the world today. Several major risk factors such as hepatitis viral infection and non-alcoholic steatohepatitis have been well established for causing liver cancer, but the contribution of environmental pollutants to liver inflammation and carcinogenesis remains poorly studied. Here, we aimed at the development of a rapid assay to test selected environmental toxicants for their potential roles in induction of inflammation and stimulation of liver tumorigenesis. By using an established kras oncogene transgenic zebrafish model for liver cancer, we tested a total of eight selected chemicals. First, using LPS (lipopolysaccharides) as a positive control, we confirmed its effects on induction of inflammation and stimulation of liver tumorigenesis as indicated by increases of neutrophils and the size of oncogenic livers respectively. Next, we tested two heavy metals (arsenic and chromium) and five organic toxicants (bisphenol A, lindane, N-nitrosodiethylamine, and 3,3,4,4,5-pentachlorobiphenyl [PCB126], and 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]). We observed a good correlation on induction of inflammation and their ability for stimulation of liver tumorigenesis. Most toxicants, namely chromium, bisphenol A, lindane, N-nitrosodiethylamine, and PCB126, resulted in increased inflammation and liver tumorigenesis, while arsenic and TCDD had opposite effects. Thus, our study established a screening system to rapidly assess the effects of candidate chemicals on liver tumorigenesis and inflammation.