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USC Study Shows Common PFAS Drive Liver Fat and Cancer-Linked Changes in Human Cells

Researchers used multi-donor 3D liver models with single-cell RNA sequencing to reveal chemical-specific, sex-differential effects.

Overview

  • PFOA and PFHxS increased fat accumulation in liver cells by distinct mechanisms, with PFOA prompting fat production and PFHxS causing fat retention.
  • PFOS and PFNA induced cancer-related gene changes, with PFNA showing the strongest impact and altering cancer-linked genes in 61.3% of exposed cells.
  • Across chemicals, the compounds disrupted cell signaling and immune functions, though the molecular shifts were specific to each PFAS.
  • Liver cells derived from female donors were more affected by PFOA, while cells from male donors were more affected by PFOS.
  • The study exposed liver spheroids from 10 donors to four PFAS for seven days, and authors say follow-up analyses are assessing mixtures and could inform tests of FDA-approved drugs that regulate liver fat.