Involvement of Per- and Polyfluoroalkyl Compounds in Tumor Development

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 2024 Mar 13

PMID 38478087

Authors

Maija Pesonen

Kirsi Vahakangas

Affiliations

Soon will be listed here.

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure.

References

Costello E, Rock S, Stratakis N, Eckel S, Walker D, Valvi D . Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis. Environ Health Perspect. 2022; 130(4):46001. PMC: 9044977. DOI: 10.1289/EHP10092. View

Shearer J, Callahan C, Calafat A, Huang W, Jones R, Sabbisetti V . Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma. J Natl Cancer Inst. 2020; 113(5):580-587. PMC: 8096365. DOI: 10.1093/jnci/djaa143. View

Maras M, Vanparys C, Muylle F, Robbens J, Berger U, Barber J . Estrogen-like properties of fluorotelomer alcohols as revealed by mcf-7 breast cancer cell proliferation. Environ Health Perspect. 2006; 114(1):100-5. PMC: 1332663. DOI: 10.1289/ehp.8149. View

Sunderland E, Hu X, Dassuncao C, Tokranov A, Wagner C, Allen J . A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects. J Expo Sci Environ Epidemiol. 2018; 29(2):131-147. PMC: 6380916. DOI: 10.1038/s41370-018-0094-1. View

Elcombe C, Elcombe B, Foster J, Chang S, Ehresman D, Butenhoff J . Hepatocellular hypertrophy and cell proliferation in Sprague-Dawley rats from dietary exposure to potassium perfluorooctanesulfonate results from increased expression of xenosensor nuclear receptors PPARα and CAR/PXR. Toxicology. 2012; 293(1-3):16-29. DOI: 10.1016/j.tox.2011.12.014. View

Kurwadkar S, Dane J, Kanel S, Nadagouda M, Cawdrey R, Ambade B . Per- and polyfluoroalkyl substances in water and wastewater: A critical review of their global occurrence and distribution. Sci Total Environ. 2021; 809:151003. PMC: 10184764. DOI: 10.1016/j.scitotenv.2021.151003. View

Dairkee S, Luciani-Torres G, Moore D, Jaffee I, Goodson 3rd W . A Ternary Mixture of Common Chemicals Perturbs Benign Human Breast Epithelial Cells More Than the Same Chemicals Do Individually. Toxicol Sci. 2018; 165(1):131-144. PMC: 6135635. DOI: 10.1093/toxsci/kfy126. View

Schrenk D, Bignami M, Bodin L, Chipman J, Del Mazo J, Grasl-Kraupp B . Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA J. 2020; 18(9):e06223. PMC: 7507523. DOI: 10.2903/j.efsa.2020.6223. View

Luo K, Liu X, Nian M, Wang Y, Qiu J, Yu H . Environmental exposure to per- and polyfluoroalkyl substances mixture and male reproductive hormones. Environ Int. 2021; 152:106496. DOI: 10.1016/j.envint.2021.106496. View

10.

Li X, Song F, Liu X, Shan A, Huang Y, Yang Z . Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population. Environ Health. 2022; 21(1):83. PMC: 9463854. DOI: 10.1186/s12940-022-00895-3. View

11.

Mesnil M, Aasen T, Boucher J, Chepied A, Cronier L, Defamie N . An update on minding the gap in cancer. Biochim Biophys Acta Biomembr. 2017; 1860(1):237-243. DOI: 10.1016/j.bbamem.2017.06.015. View

12.

Li Y, Barregard L, Xu Y, Scott K, Pineda D, Lindh C . Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water. Environ Health. 2020; 19(1):33. PMC: 7071576. DOI: 10.1186/s12940-020-00588-9. View

13.

Knutsen H, Alexander J, Barregard L, Bignami M, Bruschweiler B, Ceccatelli S . Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food. EFSA J. 2020; 16(12):e05194. PMC: 7009575. DOI: 10.2903/j.efsa.2018.5194. View

14.

Robarts D, Venneman K, Gunewardena S, Apte U . GenX induces fibroinflammatory gene expression in primary human hepatocytes. Toxicology. 2022; 477:153259. PMC: 9741548. DOI: 10.1016/j.tox.2022.153259. View

15.

Barry V, Winquist A, Steenland K . Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013; 121(11-12):1313-8. PMC: 3855514. DOI: 10.1289/ehp.1306615. View

16.

Solan M, Koperski C, Senthilkumar S, Lavado R . Short-chain per- and polyfluoralkyl substances (PFAS) effects on oxidative stress biomarkers in human liver, kidney, muscle, and microglia cell lines. Environ Res. 2023; 223:115424. DOI: 10.1016/j.envres.2023.115424. View

17.

Chou H, Wen L, Chang C, Lin C, Jin L, Juan S . From the Cover: l-Carnitine via PPARγ- and Sirt1-Dependent Mechanisms Attenuates Epithelial-Mesenchymal Transition and Renal Fibrosis Caused by Perfluorooctanesulfonate. Toxicol Sci. 2017; 160(2):217-229. DOI: 10.1093/toxsci/kfx183. View

18.

Cui Q, Pan Y, Wang J, Liu H, Yao B, Dai J . Exposure to per- and polyfluoroalkyl substances (PFASs) in serum versus semen and their association with male reproductive hormones. Environ Pollut. 2020; 266(Pt 2):115330. DOI: 10.1016/j.envpol.2020.115330. View

19.

Liu R, Hurtt M, Cook J, Biegel L . Effect of the peroxisome proliferator, ammonium perfluorooctanoate (C8), on hepatic aromatase activity in adult male Crl:CD BR (CD) rats. Fundam Appl Toxicol. 1996; 30(2):220-8. DOI: 10.1006/faat.1996.0059. View

20.

Corton J, Peters J, Klaunig J . The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions. Arch Toxicol. 2017; 92(1):83-119. PMC: 6092738. DOI: 10.1007/s00204-017-2094-7. View