Department of Occupational and Environmental Health, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, 215123, China.
School of Civil Engineering, Suzhou University of Science and Technology, 215011, China.
Environ Pollut. 2024 Apr 1;346:123574. doi: 10.1016/j.envpol.2024.123574. Epub 2024 Feb 14.
Hexafluoropropylene oxide dimer acid (GenX) is an alternative to perfluorooctanoic acid (PFOA), whose environmental concentration is close to its maximum allowable value established by the US Environmental Protection Agency, so its effects on human health are of great concern. The liver is one of the most crucial target organ for GenX, but whether GenX exposure induces liver cancer still unclear. In this research project, male C57 mice were disposed to GenX in drinking water at environmental concentrations (0.1 and 10 μg/L) and higher concentrations (1 and 100 mg/L) for 14 weeks to explore its effects on liver injury and potential carcinogenicity in mice. GenX was found to cause a dose-dependent increase in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG). As the content of GenX in drinking water increased, so did the concentrations of Glypican-3 (GPC-3) and detachment gamma-carboxyprothrombin (DCP), indicators of early hepatocellular cancer. GenX destroyed the boundaries and arrangements of hepatocytes, in which monocyte infiltration, balloon-like transformation, and obvious lipid vacuoles were observed between cells. Following exposure to GenX, Masson sections revealed a significant quantity of collagen deposition in the liver. Alpha-feto protein (AFP), vascular endothelial growth factor (VEGF), Ki67, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene expression increased in a dose-dependent manner in the treatment group relative to the control group. In general, drinking water GenX exposure induced liver function impairment, elevated blood lipid level, caused liver pathological structure damage and liver fibrosis lesions, changed the liver inflammatory microenvironment, and increased the concentration of liver-related tumor indicator even in the environmental concentration, suggesting GenX is a potential carcinogen.
全氟辛烷磺酸氧化物二聚体酸（GenX）是全氟辛酸（PFOA）的替代品，其环境浓度接近美国环境保护署规定的最大允许值，因此其对人类健康的影响备受关注。肝脏是 GenX 的最重要靶器官之一，但 GenX 暴露是否会导致肝癌尚不清楚。在本研究项目中，雄性 C57 小鼠被置于环境浓度（0.1 和 10μg/L）和更高浓度（1 和 100mg/L）的 GenX 饮用水中 14 周，以探讨其对小鼠肝脏损伤和潜在致癌性的影响。结果发现，GenX 导致血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）和甘油三酯（TG）水平呈剂量依赖性升高。随着饮用水中 GenX 含量的增加，Glypican-3（GPC-3）和脱γ-羧基凝血酶原（DCP）的浓度也升高，这是早期肝细胞癌的指标。GenX 破坏了肝细胞的边界和排列，观察到单核细胞浸润、气球样变性和细胞间明显的脂质空泡。暴露于 GenX 后，Masson 切片显示肝脏中有大量胶原沉积。与对照组相比，治疗组的α-胎蛋白（AFP）、血管内皮生长因子（VEGF）、Ki67、基质金属蛋白酶 2（MMP-2）和基质金属蛋白酶 9（MMP-9）基因表达呈剂量依赖性增加。总的来说，饮用水 GenX 暴露会导致肝功能损害、血脂水平升高、肝脏病理结构损伤和肝纤维化病变，改变肝脏炎症微环境，即使在环境浓度下也会增加与肝脏相关的肿瘤指标浓度，提示 GenX 是一种潜在的致癌物质。
