Perfluorooctanoic acid (PFOA) acts as a tumor promoter on Syrian hamster embryo (SHE) cells

Abstract

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.

Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

“…PFOA is widely used in the industrial production. It has been demonstrated that exposure to PFOA causes a variety of toxicities, including hepatotoxicity, carcinogenicity, neurotoxicity, immunotoxicity, and genotoxicity [24][25][26][27][28]. Epidemiologic studies have also shown that PFOA exposure is positively associated with cardiovascular disease [29], chronic kidney disease [30], thyroid disease [31], and hepatocellular damage [32].…”

NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid, Perfluorooctanoic Acid, Perfluorononanoic Acid, and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

“…Similar results were obtained for PFNA when tested at 0.125 or 0.25 mg/mL 95 . Exposure to PFOA at concentrations up to 300 µM for 5 or 24 hours did not induce DNA damage in Syrian hamster embryo cells as measured using the comet assay 96 . Negative results were also reported for the comet assay when freshly isolated Wistar rat testicular cells were exposed to 100 or 300 µM PFOA for 24 hours; however, a significant increase in DNA damage was observed when testicular cells were exposed to 300 µM PFNA for 24 hours 97 .…”

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

“…PFOA did not induce mutations in bacteria (Fernández Freire et al., ; Buhrke et al., ), but increased mutation frequency at CD59 loci in human hamster hybrid cells at the highest applied (cytotoxic) concentration after long‐term (16 days) incubation (Zhao et al., ). Four studies reported no genotoxic effects (DNA strand breaks, micronuclei) after PFOA treatment in HepG2 (Florentin et al., ; Eriksen et al., ), V79 (Buhrke et al., ) and SHE cells (Jacquet et al., ). Three studies reported increased micronuclei, strand breaks and 8OHdG in HepG2 (Yao and Zhong, ; Wielsøe et al., ) and TK6 cells (Yahia et al., ).…”