GenX caused liver injury and potential hepatocellular carcinoma of mice via drinking water even at environmental concentration.

Environ Pollut

Department of Occupational and Environmental Health, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, 215123, China. Electronic address:

Published: April 2024

AI Article Synopsis

  • GenX, an alternative to PFOA, has raised health concerns, particularly regarding its impact on liver health, as the potential link to liver cancer remains unclear.
  • Exposure studies in male C57 mice showed that GenX increased the serum levels of liver enzymes and cholesterol in a dose-dependent manner, indicating liver injury.
  • Significant changes in liver structure, including collagen deposition and altered inflammatory conditions, were observed, leading to the conclusion that GenX could potentially act as a carcinogen even at environmental concentrations.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.envpol.2024.123574DOI Listing

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