Laboratory Interactions Ecotoxicology Biodiversity Ecosystems, University Paul Verlaine, CNRS UMR 7146, Rue du General Delestraint, 57070, Metz, France.
Environ Sci Pollut Res Int. 2011 Aug;19(7):2537-49. doi: 10.1007/s11356-012-0968-z. Epub 2012 Aug 31.
Perfluorooctane sulfonate (PFOS) (C(8)F(17)SO(3)) and perfluorooctanoic acid (PFOA) (C(8)HF(15)O(2)) are synthetic chemicals widely used in industrial applications for their hydrophobic and oleophobic properties. They are persistent, bioaccumulative, and toxic to mammalian species. Their widespread distribution on earth and contamination of human serum raised concerns about long-term side effects. They are suspected to be carcinogenic through a nongenotoxic mode of action, a mechanism supported by recent findings that PFOS induced cell transformation but no genotoxicity in Syrian hamster embryo (SHE) cells. In the present study, we evaluated carcinogenic potential of PFOA using the cell transformation assay on SHE cells. The chemical was applied alone or in combination with a nontransformant concentration of benzo[a]pyrene (BaP, 0.4 μM) in order to detect PFOA ability to act as tumor initiator or tumor promoter. The results showed that PFOA tested alone in the range 3.7 × 10(-5) to 300 μM did not induce SHE cell transformation frequency in a 7-day treatment. On the other side, the combination BaP/PFOA induced cell transformation at all PFOA concentrations tested, which revealed synergistic effects. No genotoxicity of PFOA on SHE cells was detected using the comet assay after 5 and 24 h of exposure. No significant increase in DNA breakage was found in BaP-initiated cells exposed to PFOA in a 7-day treatment. The whole results showed that PFOA acts as a tumor promoter and a nongenotoxic carcinogen. Cell transformation in initiated cells was observed at concentrations equivalent to the ones found in human serum of nonoccupationally and occupationally exposed populations. An involvement of PFOA in increased incidence of cancer recorded in occupationally exposed population cannot be ruled out.
全氟辛烷磺酸 (PFOS) (C(8)F(17)SO(3)) 和全氟辛酸 (PFOA) (C(8)HF(15)O(2)) 是两种广泛应用于工业生产的合成化学品，因其具有疏水性和疏油性而被广泛使用。它们具有持久性、生物蓄积性和对哺乳动物物种的毒性。它们在地球上的广泛分布和对人类血清的污染引起了人们对长期副作用的关注。它们被怀疑通过非遗传毒性作用致癌，这一机制得到了最近的发现的支持，即 PFOS 诱导细胞转化，但在叙利亚仓鼠胚胎 (SHE) 细胞中没有遗传毒性。在本研究中，我们使用 SHE 细胞的细胞转化试验评估了 PFOA 的致癌潜力。该化学物质单独或与非转化浓度的苯并[a]芘 (BaP，0.4 μM) 联合应用，以检测 PFOA 作为肿瘤启动剂或肿瘤促进剂的能力。结果表明，PFOA 单独在 3.7×10(-5) 至 300 μM 的范围内在 7 天处理中不会诱导 SHE 细胞转化频率。另一方面，所有测试浓度的 BaP/PFOA 组合均诱导细胞转化，显示出协同作用。在用彗星试验检测 SHE 细胞的遗传毒性时，5 和 24 小时暴露后均未发现 PFOA 的遗传毒性。在 7 天处理中，用 PFOA 处理 BaP 起始的细胞后，未发现 DNA 断裂有显著增加。总的来说，结果表明 PFOA 是一种肿瘤促进剂和非遗传毒性致癌物质。在起始细胞中观察到的细胞转化发生在相当于职业暴露和非职业暴露人群的人类血清中发现的浓度。不能排除 PFOA 参与职业暴露人群癌症发病率增加的可能性。
