Department of Pharmacology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.
Department of Neurology, Daegu Catholic University Medical Center, Daegu 42472, Republic of Korea.
Int J Environ Res Public Health. 2023 Sep 30;20(19):6868. doi: 10.3390/ijerph20196868.
Perfluorohexane sulfonate (PFHxS) is a widely detected replacement for legacy long-chain perfluoroalkyl substances (PFAS) in the environment and human blood samples. Its potential toxicity led to its recent classification as a globally regulated persistent organic pollutant. Although animal studies have shown a positive association between PFHxS levels and hepatic steatosis and hepatocellular hypertrophy, the link with liver toxicity, including end-stage liver cancer, remains inconclusive. In this study, we examined the effects of PFHxS on the proliferation of Hep3B (human hepatocellular carcinoma) and SK-Hep1 (human liver sinusoidal endothelial cells). Cells were exposed to different PFHxS concentrations for 24-48 h to assess viability and 12-14 days to measure colony formation. The viability of both cell lines increased at PFHxS concentrations <200 μM, decreased at >400 μM, and was highest at 50 μM. Colony formation increased at <300 μM and decreased at 500 μM PFHxS. Consistent with the effect on cell proliferation, PFHxS increased the expression of proliferating cell nuclear antigen (PCNA) and cell-cycle molecules (CDK2, CDK4, cyclin E, and cyclin D1). In summary, PFHxS exhibited a biphasic effect on liver cell proliferation, promoting survival and proliferation at lower concentrations and being cytotoxic at higher concentrations. This suggests that PFHxS, especially at lower concentrations, might be associated with HCC development and progression.
全氟己烷磺酸 (PFHxS) 是一种广泛存在于环境和人体血液样本中的新型长链全氟烷基物质 (PFAS) 替代品。由于其潜在的毒性，最近将其归类为全球受管制的持久性有机污染物。尽管动物研究表明 PFHxS 水平与肝脂肪变性和肝细胞肥大之间存在正相关，但与肝毒性（包括终末期肝癌）之间的联系仍不确定。在这项研究中，我们研究了 PFHxS 对 Hep3B（人肝癌细胞）和 SK-Hep1（人肝窦内皮细胞）增殖的影响。将细胞暴露于不同浓度的 PFHxS 24-48 小时以评估细胞活力，12-14 天以测量集落形成。两种细胞系的活力在 PFHxS 浓度 <200 μM 时增加，在 >400 μM 时降低，在 50 μM 时最高。集落形成在 <300 μM 时增加，在 500 μM PFHxS 时降低。与对细胞增殖的影响一致，PFHxS 增加了增殖细胞核抗原 (PCNA) 和细胞周期分子（CDK2、CDK4、cyclin E 和 cyclin D1）的表达。总之，PFHxS 对肝细 胞增殖表现出双相作用，在较低浓度下促进存活和增殖，在较高浓度下具有细胞毒性。这表明 PFHxS，特别是在较低浓度下，可能与 HCC 的发生和发展有关。
